{"paper_id":"3f53c6b3-5dbf-45d2-8643-e12e759541a0","body_text":"Hematopoietic stem cell mobilization folowing high-intensity interval exercise in cancer patients undergoing bone marrow transplantation : A clinical randomized trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Hematopoietic stem cell mobilization folowing high-intensity interval exercise in cancer patients undergoing bone marrow transplantation : A clinical randomized trial Tayebe Zarekar, Sajad Ahmadizad, Abbas Hajifathali, Elham Roshandel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7178782/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Hematopoietic stem cells (HSCs) released from the bone marrow through mobilization have been used as a convenient source for Hematopoietic stem cell transplantation (HSCT). Exercise can mobilize HSCs into circulation in an intensity-dependent manner. Therefore, this study examined the effects of high-intensity interval exercise (HIIE) performed prior to HSCT on HSCs mobilization in autologous bone marrow transplant patients. Methods : Twenty patients were divided into two groups. To determine peak power, patients in the exercise group performed a graded exercise test. After receiving the granulocyte-colony stimulating factor, they performed a HIIE protocol included 12 × 1-min effort at 100% peak power followed by 1-min active recovery at 20% of peak power. Blood samples were taken before and immediately after exercise and analyzed for catecholamine and CD34 + . Results : Data analyses revealed significant increase (P<0.05) in epinephrine, norepinephrine, and CD34 + after exercise compare to control group. In addition, there was a positive correlation between epinephrine and CD34 + after exercise in HIIE group. CD34 + cells, and mononuclear cells, were not significantly different between two groups (p>0.05). Conclusions : It is concluded that HIIE is capable of mobilizing HSCs through increasing epinephrine. However, the increased catecholamine and CD34 + cells after HIIE did not affect the apheresis products, possibly due to HSCs time courses and homing. Epinephrine Norepinephrine Apheresis products CD34+ cells Mononuclear cells Figures Figure 1 1. Introduction Hematopoietic stem cell transplantation (HSCT) is a promising therapy for hematological malignancies such as lymphoma and multiple myeloma [ 1 ]. Peripheral blood hematopoietic stem cells (HSCs) are released from the bone marrow into peripheral blood through mobilization and have been used as a source for HSCT [ 2 ]. HSCs and primitive progenitors, are identified by their expression of the CD34 membrane phosphoglycoprotein [ 3 ]. For successful HSCT engraftment, at least 5 million CD34 + cells/Kg of recipient body weight are required [ 4 ] and receiving less than 1–2 × 10 6 CD34 + cells/kg may lead to delayed, partial, or failed engraftment [ 2 ]. The number of CD34 + cells also determines the time of apheresis [ 5 ]. Some factors such as gender, disease status before mobilization, and body surface area affect the mobilization and apheresis yield [ 5 ]. The amount of HSCs in peripheral blood follows a circadian rhythm, consistent with the rhythm of norepinephrine release, where, activation of adrenergic receptors-2 on the HSCs surface by catecholamine can increase HSCs mobilization [ 6 ]. In healthy individuals, exercise can induce HSCs mobilization and serve as an adjuvant [ 7 ]. Previous studies have confirmed that maximal exercise in the form of rowing, running, and cycling increase HSCs mobilization between 1.5-4 folds [ 8 – 10 ] in an intensity [ 9 ] and time-dependent [ 10 ] manner. The increased levels remain high shortly after exercise and return to the baseline after 30–60 min recovery [ 8 ], probably due to HSCs removal from circulation to repair the exercise-induced tissue damage [ 8 ].. In athletes a two-fold increase in CD34 + cell count has been reported after performing 1000 m rowing on an ergometer [ 11 ]. Exercise is feasible and safe lifestyle intervention for HSCT patients [ 12 ] and helps HSCs mobilization during the inpatient period [ 13 ]. However, little studies are conducted on the effect of high-intensity exercise particularly high intensity interval exercise (HIIE) in the context of HSCT [ 12 ]. It has been reported that HIIE as a discontinuous mode of exercise [ 13 ], has produced a greater change in catecholamine levels than continuous exercise [ 14 ]. Since, norepinephrine release is related to HSCs in the peripheral circulation and activation of the sympathetic nervous system is a responsible mechanism for exercise-induced mobilization of HSCs [ 7 ], we hypothesized that HIIE can mobilize more CD34 + through increasing catecholamine. Therefore, we evaluated whether patients undergoing HSCT benefit from increased CD34 + following HIIE. Additionally, to understand the mechanism of exercise-induced mobilization, we assessed any possible correlations between the changes in CD34 + and catecholamine following HIIE. 2. Materials and methods 2.1. Ethical approval Informed consent was obtained from all individual participants included in the study. This study met high standards of ethical principles for human research and has been approved by the University’s Ethics Committee (IR.SBMU.REC.1400.017). This study was conducted according to the Declaration of Helsinki. 2.2. Protocol registration Registration of this trial protocol under the scientific name of \"The effect of high-intensity interval exercise and training on the mobilization of hematopoietic stem cells in autologous bone marrow transplant patients\" has been approved in Iranian Registry of Clinical Trials at 2023-01-08. The registration reference is IRCT20230101057012N1. 2.3. Participants The study was conducted on twenty autologous hematopoietic stem cell transplantation (auto-HSCT) candidates with lymphoma and multiple myeloma who were admitted to Hospital. Patients were divided into two homogeneous groups (exercise and control groups, n=10 in each group) based on their age, type of hematological malignancies, and body mass index (BMI). Patients’ and disease characteristics are represented in Table 1. Inclusion criteria were: age range of 18-55 years old, BMI less than 30 (non-obese), non-smoker, no history of comorbidities such as cardiovascular or pulmonary disease, autonomic dysfunction, kidney disease, hepatitis, and diabetes. The exclusion criteria included: the inability to perform the exercise with determined intensity and duration, and the physician’s opinion on activity cessation due to symptoms such as chest pain, dizziness, nausea, dyspnea, and sagging ST segment. Participants were informed about the design of the study with possible risks and discomfort that might result from the study and after understanding the procedures signed a written informed consent to participate in the study. 2.4. Experimental design and protocols On the first day of hospitalization, patients performed the graded exercise test (GXT) to determine the peak power. After 5 min warm-up and stretching, the test began with an initial power of 20 watts and increased by 10 watts every minute until exhaustion. During the GXT, heart rate was measured continuously by a pulse oximeter, and patients were asked to rate their perceived exertion (RPE) at the end of each stage, based on the Borg’s 6-20 scale [15]. The test was terminated when the patient reached the perceived exertion of 20 or the maximum heart rate calculated as 220-age. For each patient the power for the final stage of the test was recorded as peak power. Systolic and diastolic blood pressure were recorded at rest by using a digital blood pressure monitor (Omron M3, Omron Healthcare Co., Ltd. Japan). Patients in both groups received granulocyte colony-stimulating factor (G-CSF) for five days. Patients in exercise group performed a HIIE protocol 6 hours after the last dose of G-CSF. HIIE included 5 min warm up at 10-20% of their peak power followed by 12 repetitions of one min cycling at 100% peak power interspersed by one-minute active recovery at 20% of peak power. Patients in the control group performed no exercise and sat for the same period of time. For both groups blood samples were taken before and immediately after the HIIE protocol. 2.5. Blood sampling and analyses Blood samples were obtained through a catheter from the cervical vein with minimum stasis and collected in EDTA tubes for complete blood counts (CBC) using an automated cell counter (Sysmex KX21, Japan) and CD34 + cell counts using a flow cytometer (BD FACS Calibur; BD biosciences, San Jose, CA). The serum specimens were obtained from centrifugation of the blood samples containing clot activator at 1500g for 10 min and immediately frozen and stored at -80ºC for subsequent catecholamine analysis. The enzyme-linked immunosorbent assay (ELISA) was performed to quantify epinephrine and norepinephrine using the human epinephrine and norepinephrine kits (ELISA Kit, MBS285087, Mybiosource, Germany). 2.6. Statistical analyses Data were analyzed by using SPSS statistics for windows, version 22.0. Shapiro-Wilk test was used to examine the distribution of data. The pre- and post-exercise values for catecholamine and CD34 + in two groups were compared using the repeated measures of ANOVA with between subject factors. The independent t-test was used to compare the patients’ characteristics and apheresis product including white blood cells (WBCs), CD34 + cells, and mononuclear cells (MNCs) between two groups. The Pearson correlation test was used to assess the correlation between post-exercise catecholamine levels and the number of mobilized CD34 + cells in the peripheral blood. P≤0.05 is considered significant. 3. Results The independent t-test indicated no significant differences ( p >0.05) between the baseline characteristics of patients in two groups (Table 1). Table 1. Patients’ general and disease characteristics Characteristics HIIE Control Number Female 4 5 Male 6 5 Non-Hodgkin Lymphoma 2 0 Hodgkin Lymphoma 5 8 Multiple Myeloma 3 2 Plerixafor administration 2 3 mean± SD Age (years) 32.2±11.6 33.1±9.5 BMI (kg/m 2 ) 27.3±4.8 25.9±9.2 HR rest (bpm) 92.5±7.7 87.5±7.6 Systolic Blood Pressure (mmHg) 121±10 113±10 Diastolic Blood Pressure (mmHg) 75.0±10.8 71.0±5.6 Time from HSCT to engraft (days) 11.4±1.7 11.1±1.6 No. of G-CSF administration (days) 5.1±1.1 5.6±1.1 No. of G-CSF administration (dose) 11.9±2.3 12.7±3.7 HIIE: High-intensity interval exercise; BMI: Body mass index; HR: Heart rate; HSCT: Hematopoietic stem cell transplantation; G-CSF: Granulocyte colony-stimulating factor. Data analysis showed a significant difference between responses of epinephrine, norepinephrine, and CD34 + in two groups (Figure 1). These variables were increased pronouncedly following HIIE in exercise group compared to control group. Besides, the Pearson’s test demonstrated a positive correlation between epinephrine levels after exercise and the number of mobilized CD34 + cells in the peripheral blood ( r =0.738, p =0.009). However, WBC count on the day before apheresis showed no significant differences between the two groups ( p >0.05). Similarly, apheresis products, including WBCs, CD34 + cells, and MNCs, showed no significant ( p >0.05) differences (Table 2). Table 2. The WBC count and apheresis content (mean± SD) on the day before apheresis. Groups HIIE Control p-value Before the apheresis: WBC (×10 3 /uL) 34.5±13.8 32.9±14.2 0.80 Apheresis product s: WBC (×10 6 cells/kg) CD34 + (×10 6 cells/kg) 10.9±4.0 4.42±1.68 12.9±5.5 4.62±2.61 0.08 0.60 MNC (×10 6 cells/kg) 7.28±1.95 7.64±2.59 0.24 HIIE: High-intensity interval exercise; WBC: White blood cells; MNC: Mononuclear cell. 4. Discussion The aim of this study was to investigate the effect of HIIE on the mobilization of HSCs in autologous HSCT patients. In our study, we observed 46% increase in CD34 + cell count after exercise in HIIE group. This result confirms that HIIE is capable of mobilizing HSCs from bone marrow to peripheral blood, which supports findings of previous studies reported the beneficial effects of exercise, as an adjunctive method, in HSCs mobilization in healthy individuals [7] and patients receiving HSCT [16,17]. A 2.5-fold increase in CD34 + cells was observed after exercise at 70% peak work rate, which confirms that HSCs mobilization after aerobic exercise is intensity related [9]. Our findings is also in line with those who demonstrated a significant rise in CD34 + cell count after 15 min of strenuous exercise compared to moderate exercise [18]. Despite reasonable number of investigations on the effects of acute exercise on HSCs mobilization, there is no consensus regarding the mechanisms and extent of effects [19]. Activation of the sympathetic nervous system is one of the main mechanisms responsible for exercise-induced mobilization of HSCs [7]. Circadian release of norepinephrine is correlated with HSCs concentration in the peripheral circulation and overnight norepinephrine variation is related to changes in HSCs function [7]. Increased epinephrine decreases the CXC motif chemokine 12 (CXCL12) expression in the bone marrow niche, which lead to increases in HSCs mobilization [7]. Furthermore, the nervous system has a negative effect on stromal cell-derived factor1 (SDF-1) and probably a positive effect on CXC chemokine receptor type 4 (CXCR4) [20]. Increased expression of proteolytic enzymes in stromal cells, inhibition of mesenchymal stem cell differentiation to osteoblasts, and higher differentiation of osteoclasts from HSCs are other mechanisms that might lead to HSCs mobilization [20]. A higher expression of neural receptors, including dopamine and beta-adrenergic receptors (β2-AR), has been detected in the primitive CD34 + CD38 low population compared to CD34 + CD38 high [20]. Exercise-induced mobilization of CD34 + HSCs is more dependent on β2-AR signaling than circulating G-CSF [18]. Similar to previous studies [21] we also found that exercise-induced increases in catecholamine can enhance stem cell mobilization during and after exercise and this rise is completely independent of G-CSF. Since in our study, the same amount of G-CSF was administrated for two groups the higher CD34 + in HIIE groups could be attributed to exercise not G-SCF. Positive correlations of post-exercise epinephrine with HSCs mobilization is another important finding of the present study. These findings were consistent with those of Stelzer et al. (2014) who reported a 10-fold accumulation of norepinephrine after a graded exercise test which was correlated with HSCs mobilization in healthy male athletes [22]. In line with this study [22], our results indicated that epinephrine and norepinephrine levels increased significantly after HIIE by 480 and 126%, respectively. Therefore, our findings support the hypothesis that the exercise-induced HSCs mobilization is triggered by catecholamine. In addition, there are some other factors that were not measured in the present study, but may explain mobilization induced by acute exercise [23]. The HIIE increased several pro-angiogenic factors and enhanced nitric oxide metabolites availability that might play a role in exercise-induced mobilization [23]. HIIE, as a discontinuous mode of exercise with repeated short bouts of high intensity exercise, interspersed by low intensity exercise [13], has resulted in higher hemodynamic responses compared to a moderate continuous exercise [24]. Increased hemodynamic responses can increase blood flow and the shear-stress-induced nitric oxide metabolites bioavailability [25]. On the other hand, exercise-induced inflammation increases HSCs in the peripheral blood, where they are later mobilized to the spleen [7]. It has been shown that IL-6, a primary mediator of this inflammatory response increased up to 100-fold following exercise [7]. Moreover, stabilization of hypoxia inducible factor-1α (HIF-1α), a regulator of cell response to hypoxia, can enhance mobilization through vasodilatation of sinusoids due to increased VEGF levels, with resultant increase in mobilization [26]. Therefore, HSCs mobilization in the present study might be explained by HIIE-induced increases in the expression level of HIF-1α [27] and inflammatory markers. We found that a session of HIIE before apheresis did not affect the CD34 + cell count in the apheresis product. Saba et al. (2013) determined a time course for HSCs mobilization after the cycle ergometer test with an increase in circulating hematopoietic progenitor cells after 10 min of recovery, and a return to the baseline at 30, 60, and 120 min post-exercise [28]. On the other hand, it has been shown that the hematopoietic stem and progenitor cell levels increase 0–5 min after exercise, with no changes after 6–20 min [19]. Similarly, another study reported no changes in circulating HSCs count 0.5, 1, and 3 h after exercise [19]. Therefore, it might be concluded that exercise-induced increases in HSCs is transient and returns to baseline shortly after exercise. In the present study, although the CD34 + cell count was significantly higher in the HIIE group no significant difference in apheresis content was found, which might prove temporary increases in CD34 + cell count and dropped drop to baseline during the apheresis process. Lastly, consistent with our results, 20 min of regular exercise during mobilization could not significantly increase the CD34 + level in the apheresis product [17]. This is likely due to the effect of exercise on specific subsets of CD34 + cells [17]. Certain chemotherapeutic agents in the conditioning regimen and exercise-induced ischemia might have masked the positive impact of exercise on the number of mobilized stem cells [17]. Future research is needed to find out the optimum intensity, duration, and frequency for the optimization of HSCs mobilization. 5. Conclusions Generally, based on the findings of the present study, it could be concluded that one session of HIIE induces HSCs mobilization in auto-HSCT patients through increases induced in epinephrine levels and elevated levels of CD34 + cell count immediately after exercise. However, this is a transient increase and returns to baseline during the apheresis procedure, which, might suggest to shorten the time point between exercise and apheresis. Abbreviations BMI: body mass index CBC: complete blood counts CXCL12: CXC motif chemokine 12 CXCR4: CXC chemokine receptor type 4 ELISA: enzyme-linked immunosorbent assay G-CSF: granulocyte colony-stimulating factor GXT: graded exercise test HIF-1α: hypoxia inducible factor-1α HIIE: high intensity interval exercise HSCs: hematopoietic stem cells HSCT: hematopoietic stem cell transplantation RPE: rate of perceived exertion SDF-1: stromal cell-derived factor1 WBCs: white blood cells Declarations Acknowledgment Our special thanks to the participants and medical staff in bone marrow transplant center, Taleghani Hospital without whom fulfilling this study would not have been possible. Their contributions are sincerely appreciated and gratefully acknowledged. Ethics approval Informed consent was obtained from all individual participants included in the study. This study met high standards of ethical principles for human research and has been approved by the University’s Ethics Committee (IR.SBMU.REC.1400.017). This study was conducted according to the Declaration of Helsinki. Authors' contributions TZ, SA, and AH were responsible for the conceptualization and study design. TZ conducted experiments and SA contributed to the acquisition of data. All authors assisted with data analysis and interpretation of findings. TZ drafted the manuscript. SA and ER provided critical revision of the manuscript for important intellectual content. TZ contributed to the acquisition of data and writing the manuscript. All authors critically reviewed the content and approved the final version for publication. Conflict of interest The authors have no competing interests to declare that are relevant to the content of this article. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7178782\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":535164982,\"identity\":\"5511cf3f-9c34-4573-8551-7a7dc768eafc\",\"order_by\":0,\"name\":\"Tayebe Zarekar\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shahid Beheshti University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Tayebe\",\"middleName\":\"\",\"lastName\":\"Zarekar\",\"suffix\":\"\"},{\"id\":535164983,\"identity\":\"641c93d1-e0ca-434d-a6dc-c38dd3698ed3\",\"order_by\":1,\"name\":\"Sajad 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11:47:36\",\"extension\":\"html\",\"order_by\":14,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":89011,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"earlyproof.html\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7178782/v1/37583994e79f5d68d5199039.html\"},{\"id\":94916816,\"identity\":\"6d4561fd-1657-4cd1-b10e-0e4e12051317\",\"added_by\":\"auto\",\"created_at\":\"2025-11-01 11:47:35\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":13551,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cem\\u003e\\u003cstrong\\u003eEpinephrine (A), norepinephrine (B), and CD34\\u003c/strong\\u003e\\u003c/em\\u003e\\u003csup\\u003e\\u003cem\\u003e\\u003cstrong\\u003e+\\u003c/strong\\u003e\\u003c/em\\u003e\\u003c/sup\\u003e\\u003cem\\u003e\\u003cstrong\\u003e (C) levels (mean± SD) pre- and post-exercise.\\u003c/strong\\u003e\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003e\\u003cstrong\\u003eHIIE: High-intensity interval exercise. * Shows statistically significant difference with control group (p\\u0026lt;0.05).\\u003c/strong\\u003e\\u003c/em\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7178782/v1/90f2bc11b84ff977cf8f9ce9.png\"},{\"id\":95645032,\"identity\":\"9101cb8b-2c4a-493f-89e1-ba045c46e27d\",\"added_by\":\"auto\",\"created_at\":\"2025-11-11 14:08:18\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":894986,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7178782/v1/56855713-1ff5-4dc4-a4bc-a29ccfc47de8.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Hematopoietic stem cell mobilization folowing high-intensity interval exercise in cancer patients undergoing bone marrow transplantation : A clinical randomized trial \",\"fulltext\":[{\"header\":\"1. Introduction\",\"content\":\"\\u003cp\\u003eHematopoietic stem cell transplantation (HSCT) is a promising therapy for hematological malignancies such as lymphoma and multiple myeloma [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Peripheral blood hematopoietic stem cells (HSCs) are released from the bone marrow into peripheral blood through mobilization and have been used as a source for HSCT [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. HSCs and primitive progenitors, are identified by their expression of the CD34 membrane phosphoglycoprotein [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. For successful HSCT engraftment, at least 5\\u0026nbsp;million CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells/Kg of recipient body weight are required [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e] and receiving less than 1\\u0026ndash;2 \\u0026times; 10\\u003csup\\u003e6\\u003c/sup\\u003e CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells/kg may lead to delayed, partial, or failed engraftment [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. The number of CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells also determines the time of apheresis [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. Some factors such as gender, disease status before mobilization, and body surface area affect the mobilization and apheresis yield [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. The amount of HSCs in peripheral blood follows a circadian rhythm, consistent with the rhythm of norepinephrine release, where, activation of adrenergic receptors-2 on the HSCs surface by catecholamine can increase HSCs mobilization [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eIn healthy individuals, exercise can induce HSCs mobilization and serve as an adjuvant [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. Previous studies have confirmed that maximal exercise in the form of rowing, running, and cycling increase HSCs mobilization between 1.5-4 folds [\\u003cspan additionalcitationids=\\\"CR9\\\" citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e] in an intensity [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e] and time-dependent [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e] manner. The increased levels remain high shortly after exercise and return to the baseline after 30\\u0026ndash;60 min recovery [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e], probably due to HSCs removal from circulation to repair the exercise-induced tissue damage [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e].. In athletes a two-fold increase in CD34\\u003csup\\u003e+\\u003c/sup\\u003e cell count has been reported after performing 1000 m rowing on an ergometer [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. Exercise is feasible and safe lifestyle intervention for HSCT patients [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e] and helps HSCs mobilization during the inpatient period [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. However, little studies are conducted on the effect of high-intensity exercise particularly high intensity interval exercise (HIIE) in the context of HSCT [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. It has been reported that HIIE as a discontinuous mode of exercise [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e], has produced a greater change in catecholamine levels than continuous exercise [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. Since, norepinephrine release is related to HSCs in the peripheral circulation and activation of the sympathetic nervous system is a responsible mechanism for exercise-induced mobilization of HSCs [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e], we hypothesized that HIIE can mobilize more CD34\\u003csup\\u003e+\\u003c/sup\\u003e through increasing catecholamine. Therefore, we evaluated whether patients undergoing HSCT benefit from increased CD34\\u003csup\\u003e+\\u003c/sup\\u003e following HIIE. Additionally, to understand the mechanism of exercise-induced mobilization, we assessed any possible correlations between the changes in CD34\\u003csup\\u003e+\\u003c/sup\\u003e and catecholamine following HIIE.\\u003c/p\\u003e\"},{\"header\":\"2. Materials and methods\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.1. Ethical approval\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eInformed consent was obtained from all individual participants included in the study. This study met high standards of ethical principles for human research and has been approved by the University’s Ethics Committee (IR.SBMU.REC.1400.017). This study was conducted according to the Declaration of Helsinki.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.2. Protocol registration\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eRegistration of this trial protocol under the scientific name of\\u0026nbsp;\\\"The effect of high-intensity interval exercise and training on the mobilization of hematopoietic stem cells in autologous bone marrow transplant patients\\\"\\u0026nbsp;has been approved in Iranian Registry of Clinical Trials at 2023-01-08.\\u0026nbsp; The registration reference is IRCT20230101057012N1.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.3. Participants\\u003c/em\\u003e\\u003c/strong\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eThe study was conducted on twenty autologous hematopoietic stem cell transplantation (auto-HSCT) candidates with lymphoma and multiple myeloma who were admitted to Hospital. Patients were divided into two homogeneous groups (exercise and control groups, n=10 in each group) based on their age, type of hematological malignancies, and body mass index (BMI). Patients’ and\\u0026nbsp;disease characteristics are represented in Table 1. Inclusion criteria were: age range of 18-55 years old, BMI less than 30 (non-obese), non-smoker, no history of comorbidities such as cardiovascular or pulmonary disease, autonomic dysfunction, kidney disease, hepatitis, and diabetes. The exclusion criteria included: the inability to perform the exercise with determined intensity and duration, and the physician’s opinion on activity cessation due to symptoms such as chest pain, dizziness, nausea, dyspnea, and sagging ST segment. Participants were informed about the design of the study with possible risks and discomfort that might result from the study and after understanding the procedures signed a written informed consent to participate in the study.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.4. Experimental design and protocols\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eOn the first day of hospitalization, patients performed the graded exercise test (GXT) to determine the peak power. After 5 min warm-up and stretching, the test began with an initial power of 20 watts and increased by 10 watts every minute until exhaustion. During the GXT, heart rate was measured continuously by a pulse oximeter, and patients were asked to rate their perceived exertion (RPE) at the end of each stage, based on the Borg’s 6-20 scale [15].\\u0026nbsp;The test was terminated when the patient reached the perceived exertion of 20 or the maximum heart rate calculated as 220-age. For each patient the power for the final stage of the test was recorded as peak power.\\u0026nbsp;Systolic and diastolic blood pressure were recorded at rest by using a digital blood pressure monitor (Omron M3, Omron Healthcare Co., Ltd. Japan).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003ePatients in both groups received granulocyte colony-stimulating factor (G-CSF) for five days. Patients in exercise group performed a HIIE protocol 6 hours after the last dose of G-CSF. HIIE included 5 min warm up at 10-20% of their peak power followed by 12 repetitions of one min cycling at 100% peak power interspersed by one-minute active recovery at 20% of peak power. Patients in the control group performed no exercise and sat for the same period of time. For both groups blood samples were taken before and immediately after the HIIE protocol.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.5. Blood sampling and analyses\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eBlood samples were obtained\\u0026nbsp;through a catheter from the\\u0026nbsp;cervical\\u0026nbsp;vein with minimum stasis and collected in EDTA tubes for complete blood counts (CBC) using an automated cell counter (Sysmex KX21, Japan) and CD34\\u003csup\\u003e+\\u0026nbsp;\\u003c/sup\\u003ecell counts using a flow cytometer (BD FACS Calibur; BD biosciences, San Jose, CA). The serum specimens were obtained from centrifugation of the blood samples containing clot activator at 1500g for 10 min and immediately frozen and stored at -80ºC for subsequent catecholamine analysis. The enzyme-linked immunosorbent assay (ELISA) was performed to quantify epinephrine and norepinephrine using the human epinephrine and norepinephrine kits (ELISA Kit,\\u0026nbsp;MBS285087, Mybiosource, Germany).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2.6. Statistical analyses\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eData were\\u0026nbsp;analyzed by using SPSS statistics for windows, version 22.0. Shapiro-Wilk test was used to examine the distribution of data. The pre- and post-exercise values for catecholamine and CD34\\u003csup\\u003e+\\u003c/sup\\u003e in two groups were compared using the repeated measures of ANOVA with between subject factors. The independent t-test was used to compare the patients’ characteristics and apheresis product including\\u0026nbsp;white blood cells (WBCs), CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells, and mononuclear cells (MNCs)\\u0026nbsp;between two groups. The Pearson correlation test was used to assess the correlation between post-exercise\\u0026nbsp;catecholamine\\u0026nbsp;levels and the number of mobilized CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells in the peripheral blood. P≤0.05 is considered significant.\\u003c/p\\u003e\"},{\"header\":\"3. Results\",\"content\":\"\\u003cp\\u003eThe independent t-test indicated no significant differences (\\u003cem\\u003ep\\u003c/em\\u003e\\u0026gt;0.05) between the baseline characteristics of patients in two groups (Table 1).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eTable 1. Patients\\u0026rsquo; general and disease characteristics\\u0026nbsp;\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"586\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eCharacteristics\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eHIIE\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eControl\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003e\\n \\u003cp\\u003eNumber\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eFemale\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMale\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNon-Hodgkin Lymphoma\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eHodgkin Lymphoma\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMultiple Myeloma\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePlerixafor administration\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"2\\\" valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003e\\n \\u003cp\\u003emean\\u0026plusmn; SD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAge (years)\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e32.2\\u0026plusmn;11.6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e33.1\\u0026plusmn;9.5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBMI (kg/m\\u003csup\\u003e2\\u003c/sup\\u003e)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e27.3\\u0026plusmn;4.8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e25.9\\u0026plusmn;9.2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eHR \\u003csub\\u003erest\\u003c/sub\\u003e (bpm)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e92.5\\u0026plusmn;7.7\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e87.5\\u0026plusmn;7.6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSystolic Blood Pressure (mmHg)\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e121\\u0026plusmn;10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e113\\u0026plusmn;10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eDiastolic Blood Pressure (mmHg)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e75.0\\u0026plusmn;10.8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e71.0\\u0026plusmn;5.6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTime from HSCT to engraft \\u0026nbsp;(days)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e11.4\\u0026plusmn;1.7\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e11.1\\u0026plusmn;1.6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNo. of G-CSF administration (days)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e5.1\\u0026plusmn;1.1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e5.6\\u0026plusmn;1.1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 302px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNo. of G-CSF administration (dose)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003e11.9\\u0026plusmn;2.3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\n \\u003cp\\u003e12.7\\u0026plusmn;3.7\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eHIIE: High-intensity interval exercise; BMI: Body mass index; HR: Heart rate; HSCT: Hematopoietic stem cell transplantation; G-CSF: Granulocyte colony-stimulating factor.\\u003c/p\\u003e\\n\\u003cp\\u003eData analysis\\u0026nbsp;showed a significant difference between responses of epinephrine, norepinephrine, and CD34\\u003csup\\u003e+\\u003c/sup\\u003e in two groups (Figure 1). These variables were increased pronouncedly following HIIE in exercise group compared to control group. Besides, the Pearson\\u0026rsquo;s test demonstrated a positive correlation between epinephrine levels after exercise and the number of mobilized CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells in the peripheral blood (\\u003cem\\u003er\\u003c/em\\u003e=0.738, \\u003cem\\u003ep\\u003c/em\\u003e=0.009).\\u003c/p\\u003e\\n\\u003cp\\u003eHowever, WBC count on the day before apheresis showed no significant differences between the two groups (\\u003cem\\u003ep\\u003c/em\\u003e\\u0026gt;0.05). Similarly, apheresis products, including WBCs, CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells, and MNCs, showed no significant (\\u003cem\\u003ep\\u003c/em\\u003e\\u0026gt;0.05) differences (Table 2).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eTable 2. The WBC count and apheresis content (mean\\u0026plusmn; SD) on the day before apheresis.\\u0026nbsp;\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eGroups\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eHIIE\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eControl\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 68px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep-value\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBefore the apheresis:\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 68px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eWBC (\\u0026times;10\\u003csup\\u003e3\\u003c/sup\\u003e/uL)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e34.5\\u0026plusmn;13.8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e32.9\\u0026plusmn;14.2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 68px;\\\"\\u003e\\n \\u003cp\\u003e0.80\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eApheresis\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;product\\u003c/strong\\u003e\\u003cstrong\\u003es:\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 68px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eWBC (\\u0026times;10\\u003csup\\u003e6\\u003c/sup\\u003ecells/kg)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eCD34\\u003csup\\u003e+\\u003c/sup\\u003e (\\u0026times;10\\u003csup\\u003e6\\u003c/sup\\u003ecells/kg)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e10.9\\u0026plusmn;4.0\\u003c/p\\u003e\\n \\u003cp\\u003e4.42\\u0026plusmn;1.68\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e12.9\\u0026plusmn;5.5\\u003c/p\\u003e\\n \\u003cp\\u003e4.62\\u0026plusmn;2.61\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 68px;\\\"\\u003e\\n \\u003cp\\u003e0.08\\u003c/p\\u003e\\n \\u003cp\\u003e0.60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMNC (\\u0026times;10\\u003csup\\u003e6\\u003c/sup\\u003ecells/kg)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\n \\u003cp\\u003e7.28\\u0026plusmn;1.95\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\n \\u003cp\\u003e7.64\\u0026plusmn;2.59\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 68px;\\\"\\u003e\\n \\u003cp\\u003e0.24\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eHIIE: High-intensity interval exercise; WBC: White blood cells; MNC: Mononuclear cell.\\u003c/p\\u003e\"},{\"header\":\"4. Discussion\",\"content\":\"\\u003cp\\u003eThe aim of this study was to investigate the effect of HIIE on the mobilization of HSCs in autologous HSCT patients.\\u0026nbsp;In our study, we observed 46% increase in CD34\\u003csup\\u003e+\\u003c/sup\\u003e cell count after exercise in HIIE group.\\u0026nbsp;This result confirms that HIIE is capable of mobilizing HSCs from bone marrow to peripheral blood, which supports\\u0026nbsp;findings of\\u0026nbsp;previous studies reported the beneficial effects of exercise, as an adjunctive method, in HSCs mobilization in healthy individuals\\u0026nbsp;[7]\\u0026nbsp;and patients receiving HSCT\\u0026nbsp;[16,17].\\u0026nbsp;A 2.5-fold increase in CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells was observed after exercise at 70% peak work rate, which confirms that HSCs mobilization after aerobic exercise is intensity related\\u0026nbsp;[9]. Our findings is also in line with those who demonstrated\\u0026nbsp;a significant rise in CD34\\u003csup\\u003e+\\u003c/sup\\u003e cell count after 15 min of strenuous exercise compared to moderate exercise\\u0026nbsp;[18].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eDespite reasonable number of investigations on the effects of acute exercise on HSCs mobilization, there is no consensus regarding the mechanisms and extent of effects [19].\\u0026nbsp;Activation of the sympathetic nervous system is one of the main mechanisms responsible for exercise-induced mobilization of HSCs [7].\\u0026nbsp;Circadian release of norepinephrine is correlated with HSCs concentration in the peripheral circulation and overnight norepinephrine variation is related to changes in HSCs function [7].\\u0026nbsp;Increased epinephrine decreases the\\u0026nbsp;CXC motif chemokine 12\\u0026nbsp;(CXCL12) expression in the bone marrow niche, which lead to increases in HSCs mobilization\\u0026nbsp;[7]. Furthermore, the nervous system has a negative effect on stromal cell-derived factor1 (SDF-1) and probably a positive effect on CXC chemokine receptor type 4 (CXCR4) [20]. Increased expression of proteolytic enzymes in stromal cells, inhibition of mesenchymal stem cell differentiation to osteoblasts, and higher differentiation of osteoclasts from HSCs are other mechanisms that might lead to HSCs mobilization\\u0026nbsp;[20].\\u0026nbsp;A higher expression of neural receptors, including dopamine and beta-adrenergic receptors (β2-AR), has been detected in the primitive CD34\\u003csup\\u003e+\\u003c/sup\\u003eCD38\\u003csup\\u003elow\\u003c/sup\\u003e population compared to CD34\\u003csup\\u003e+\\u003c/sup\\u003eCD38 \\u003csup\\u003ehigh\\u003c/sup\\u003e [20].\\u0026nbsp;Exercise-induced mobilization of CD34\\u003csup\\u003e+\\u003c/sup\\u003e HSCs is more dependent on β2-AR signaling than circulating G-CSF\\u0026nbsp;[18].\\u0026nbsp;Similar to previous studies\\u0026nbsp;[21]\\u0026nbsp;we also found\\u0026nbsp;that exercise-induced increases in catecholamine can enhance stem cell mobilization during and after exercise and this rise is completely independent of G-CSF.\\u0026nbsp;Since in our study, the same amount of G-CSF was administrated for two groups the higher CD34\\u003csup\\u003e+\\u003c/sup\\u003e in HIIE groups could be attributed\\u0026nbsp;to exercise not G-SCF.\\u003c/p\\u003e\\n\\u003cp\\u003ePositive correlations of post-exercise epinephrine with HSCs mobilization is another important finding of the present study. These findings were consistent with those of\\u0026nbsp;Stelzer et al. (2014) who reported a 10-fold accumulation of norepinephrine after a graded exercise test which was correlated with HSCs mobilization in healthy male athletes [22]. In line with this study [22], our\\u0026nbsp;results indicated that\\u0026nbsp;epinephrine and norepinephrine\\u0026nbsp;levels increased significantly after HIIE by 480\\u0026nbsp;and 126%,\\u0026nbsp;respectively.\\u0026nbsp;Therefore, our findings support the hypothesis that the exercise-induced HSCs mobilization is triggered by catecholamine.\\u003c/p\\u003e\\n\\u003cp\\u003eIn addition, there are some other factors that were not measured in the present study, but may explain mobilization\\u0026nbsp;induced by acute exercise [23]. The HIIE increased several pro-angiogenic factors and enhanced nitric oxide metabolites availability that might play a role in exercise-induced mobilization [23]. HIIE, as a discontinuous mode of exercise with repeated short bouts of high intensity exercise, interspersed by low intensity exercise [13], has resulted in higher hemodynamic responses compared to a moderate continuous exercise [24]. Increased hemodynamic responses can increase blood flow and the shear-stress-induced nitric oxide metabolites bioavailability [25].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eOn the other hand, exercise-induced inflammation increases HSCs in the peripheral blood, where they are later mobilized to the spleen [7]. It has been shown that IL-6, a primary mediator of this inflammatory response increased up to 100-fold following exercise [7]. Moreover, stabilization of hypoxia inducible factor-1α (HIF-1α), a regulator of cell response to hypoxia, can enhance mobilization through vasodilatation of sinusoids due to increased VEGF levels, with resultant increase in mobilization [26]. Therefore, HSCs mobilization in the present study might be explained by HIIE-induced increases in the expression level of HIF-1α [27] and inflammatory markers.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eWe found that a session of HIIE before apheresis did not affect the CD34\\u003csup\\u003e+\\u003c/sup\\u003e cell count in the apheresis product. Saba et al. (2013)\\u0026nbsp;determined a\\u0026nbsp;time course for HSCs mobilization after the cycle ergometer test with an increase in circulating hematopoietic progenitor cells after 10 min of recovery, and a return to the baseline at 30, 60, and 120 min post-exercise [28]. On the other hand, it has been shown that the hematopoietic stem and progenitor cell levels increase 0–5 min after exercise, with no changes after 6–20 min [19]. Similarly, another study reported no changes in circulating HSCs count 0.5, 1, and 3 h after exercise [19]. Therefore, it might be concluded that exercise-induced increases in HSCs is transient and returns to baseline shortly after exercise. In the present study, although the CD34\\u003csup\\u003e+\\u003c/sup\\u003e cell count was significantly higher in the HIIE group\\u0026nbsp;no significant difference\\u0026nbsp;in apheresis content\\u0026nbsp;was found,\\u0026nbsp;which might prove temporary increases in CD34\\u003csup\\u003e+\\u003c/sup\\u003e cell count and dropped drop\\u0026nbsp;to baseline during the apheresis process.\\u003c/p\\u003e\\n\\u003cp\\u003eLastly, consistent with our results, 20 min of regular exercise during mobilization could not significantly increase the CD34\\u003csup\\u003e+\\u003c/sup\\u003e level in the apheresis product [17].\\u0026nbsp;This is likely due to the effect of exercise on specific subsets of CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells [17]. Certain chemotherapeutic agents in the conditioning regimen and exercise-induced ischemia might have masked the positive impact of exercise on the number of mobilized stem cells [17]. Future research is needed to find out the optimum intensity, duration, and frequency for the optimization of HSCs mobilization.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"5. Conclusions\",\"content\":\"\\u003cp\\u003eGenerally, based on the findings of the present study, it could be concluded that one session of HIIE induces HSCs mobilization in auto-HSCT patients through increases induced in epinephrine levels and elevated levels of CD34\\u003csup\\u003e+\\u003c/sup\\u003e cell count immediately after exercise. However, this is a transient increase and returns to baseline during the apheresis procedure, which, might suggest to shorten the time point between exercise and apheresis.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eBMI: body mass index\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eCBC: complete blood counts\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eCXCL12: CXC motif chemokine 12\\u003c/p\\u003e\\n\\u003cp\\u003eCXCR4: \\u0026nbsp;CXC chemokine receptor type 4\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eELISA: enzyme-linked immunosorbent assay\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eG-CSF: granulocyte colony-stimulating factor\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eGXT: graded exercise test\\u003c/p\\u003e\\n\\u003cp\\u003eHIF-1α: hypoxia inducible factor-1α\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eHIIE: high intensity interval exercise\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eHSCs: hematopoietic stem cells\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eHSCT: hematopoietic stem cell transplantation\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eRPE: rate of perceived exertion\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eSDF-1: stromal cell-derived factor1\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eWBCs: white blood cells\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgment\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eOur special thanks to the participants and medical staff in bone marrow transplant center, Taleghani Hospital without whom fulfilling this study would not have been possible. Their contributions are sincerely appreciated and gratefully acknowledged.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eEthics approval\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eInformed consent was obtained from all individual participants included in the study. This study met high standards of ethical principles for human research and has been approved by the University\\u0026rsquo;s Ethics Committee (IR.SBMU.REC.1400.017). This study was conducted according to the Declaration of Helsinki.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e\\u0026nbsp;Authors\\u0026apos; contributions\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTZ, SA, and AH were responsible for the conceptualization and study design. TZ conducted experiments and SA contributed to the acquisition of data. All authors assisted with data analysis and interpretation of findings. TZ drafted the manuscript. SA and ER provided critical revision of the manuscript for important intellectual content. TZ contributed to the acquisition of data and writing the manuscript. All authors critically reviewed the content and approved the final version for publication.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eConflict of interest\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors have no competing interests to declare that are relevant to the content of this article.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eRole of the Funding Source\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis work was partially supported by Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData availability\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eDuong HK, Savani BN, Copelan E, et al. Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biology of Blood and Marrow Transplantation 2014;20:1262-73. https://doi.org/10.1016/j.bbmt.2014.05.003.\\u003c/li\\u003e\\n\\u003cli\\u003eDevine H, Tierney DK, Schmit-Pokorny K, McDermott K. Mobilization of hematopoietic stem cells for use in autologous transplantation. Clinical journal of oncology nursing 2010;14. https://doi.org/10.1188/10.cjon.212-222.\\u003c/li\\u003e\\n\\u003cli\\u003eNovelli EM, Ramirez M, Civin CI. Biology of CD34+ CD38-cells in lymphohematopoiesis. Leukemia \\u0026amp; lymphoma 1998;31:285-93. https://doi.org/10.3109/10428199809059221.\\u003c/li\\u003e\\n\\u003cli\\u003eGianni AM. Where do we stand with respect to the use of peripheral blood progenitor cells?. Annals of oncology 1994;5:781-4. https://doi.org/10.1093/oxfordjournals.annonc.a059003.\\u003c/li\\u003e\\n\\u003cli\\u003eChen X, Guo Z, Chen L, et al. Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells. Chinese Journal of Tissue Engineering Research 2021;25:2958.\\u003c/li\\u003e\\n\\u003cli\\u003eM\\u0026eacute;ndez‐Ferrer S, Battista M, Frenette PS. Cooperation of \\u0026beta;2‐and \\u0026beta;3‐adrenergic receptors in hematopoietic progenitor cell mobilization. Annals of the New York Academy of Sciences 2010;1192:139-44. https://doi.org/10.1111/j.1749-6632.2010.05390.x.\\u003c/li\\u003e\\n\\u003cli\\u003eEmmons R, Niemiro GM, De Lisio M. Exercise as an adjuvant therapy for hematopoietic stem cell mobilization. Stem cells international 2016;2016. https://doi.org/10.1155/2016/7131359.\\u003c/li\\u003e\\n\\u003cli\\u003eBoppart MD, De Lisio M, Witkowski S. Exercise and stem cells. Progress in molecular biology and translational science 2015;135:423-56. https://doi.org/10.1016/bs.pmbts.2015.07.005.\\u003c/li\\u003e\\n\\u003cli\\u003e9. Baker JM, Nederveen JP, Parise G. Aerobic exercise in humans mobilizes HSCs in an intensity-dependent manner. Journal of Applied Physiology 2017;122:182-90. https://doi.org/10.1152/japplphysiol.00696.2016.\\u003c/li\\u003e\\n\\u003cli\\u003eM\\u0026ouml;bius-Winkler S, Hilberg T, Menzel K, Golla E, Burman A, Schuler G, Adams V. Time-dependent mobilization of circulating progenitor cells during strenuous exercise in healthy individuals. Journal of Applied Physiology 2009;107:1943-50. https://doi.org/10.1152/japplphysiol.00532.2009.\\u003c/li\\u003e\\n\\u003cli\\u003eMorici G, Zangla D, Santoro A, et al. Supramaximal exercise mobilizes hematopoietic progenitors and reticulocytes in athletes. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2005;289:R1496-503. https://doi.org/10.1152/ajpregu.00338.2005.\\u003c/li\\u003e\\n\\u003cli\\u003eAziz JA, Smith C, Slobodian M, Du I, Shorr R, De Lisio M, Allan DS. Impact of exercise training on hematological outcomes following hematopoietic cell transplantation: a scoping review. Clinical and Investigative Medicine 2021;44:E19-26. https://doi.org/10.25011/cim.v44i2.36369.\\u003c/li\\u003e\\n\\u003cli\\u003eMeyer P, Gayda M, Juneau M, Nigam A. High-intensity aerobic interval exercise in chronic heart failure. Current heart failure reports 2013;10:130-8. https://doi.org/10.1007/s11897-013-0130-3.\\u003c/li\\u003e\\n\\u003cli\\u003eTschakert G, Kroepfl JM, Mueller A, et al. Acute physiological responses to short-and long-stage high-intensity interval exercise in cardiac rehabilitation: a pilot study. Journal of sports science \\u0026amp; medicine 2016;15:80. https://pubmed.ncbi.nlm.nih.gov/26957930/\\u003c/li\\u003e\\n\\u003cli\\u003eBorg GA. Psychophysical bases of perceived exertion. Medicine \\u0026amp; science in sports \\u0026amp; exercise 1982; 14:377\\u0026ndash;381\\u003c/li\\u003e\\n\\u003cli\\u003eKasravi K, Ghazalian F, Gaeini A, Hajifathali A, Gholami M. A Comparison of the Effect of Two Types of Continuous and Discontinuous Aerobic Exercise on Patients\\u0026apos; Stem Cell Mobilization before Autologous Hematopoietic Stem Cell Transplantation. International Journal of Hematology-Oncology and Stem Cell Research 2021;15:61. https://doi.org/10.18502/ijhoscr.v15i1.5250.\\u003c/li\\u003e\\n\\u003cli\\u003eKeser I, Suyani E, Aki SZ, Sucak AG. The positive impact of regular exercise program on stem cell mobilization prior to autologous stem cell transplantation. Transfusion and Apheresis Science 2013;49:302-6. https://doi.org/10.1016/j.transci.2013.06.007.\\u003c/li\\u003e\\n\\u003cli\\u003eAgha NH, Baker FL, Kunz HE, Graff R, Azadan R, Dolan C, Laughlin MS, Hosing C, Markofski MM, Bond RA, Bollard CM. Vigorous exercise mobilizes CD34+ hematopoietic stem cells to peripheral blood via the \\u0026beta;2-adrenergic receptor. Brain, behavior, and immunity 2018;68:66-75. https://doi.org/10.1016/j.bbi.2017.10.001.\\u003c/li\\u003e\\n\\u003cli\\u003eSchmid M, Kroepfl JM, Spengler CM. Changes in circulating stem and progenitor cell numbers following acute exercise in healthy human subjects: a systematic review and meta-analysis. Stem Cell Reviews and Reports 2021:1-30. https://doi.org/10.1007/s12015-020-10105-7.\\u003c/li\\u003e\\n\\u003cli\\u003eSaba F, Soleimani M, Atashi A,et al. The role of the nervous system in hematopoietic stem cell mobilization. Lab Hematol 2013;19:8-16. https://doi.org/10.1532/lh96.12013.\\u003c/li\\u003e\\n\\u003cli\\u003eBigley AB, Rezvani K, Chew C, et al. Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells. Brain, behavior, and immunity 2014;39:160-71. https://doi.org/10.1016/j.bbi.2013.10.030.\\u003c/li\\u003e\\n\\u003cli\\u003eKr\\u0026ouml;pfl JM, Stelzer I, Mangge H, et al. Exercise-induced norepinephrine decreases circulating hematopoietic stem and progenitor cell colony-forming capacity. PLoS One 2014;9:e106120. https://doi.org/10.1371/journal.pone.0106120. \\u003c/li\\u003e\\n\\u003cli\\u003eFerentinos P, Tsakirides C, Swainson M, et al. The impact of different forms of exercise on endothelial progenitor cells in healthy populations. European Journal of Applied Physiology 2022;122:1589-625. https://doi.org/10.1007/s00421-022-04921-7.\\u003c/li\\u003e\\n\\u003cli\\u003eFalz R, Fikenzer S, Holzer R, Laufs U, Fikenzer K, Busse M. Acute cardiopulmonary responses to strength training, high-intensity interval training and moderate-intensity continuous training. European Journal of Applied Physiology 2019;119:1513-23. https://doi.org/10.1007/s00421-019-04138-1.\\u003c/li\\u003e\\n\\u003cli\\u003eWisl\\u0026oslash;ff U, St\\u0026oslash;ylen A, Loennechen JP, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation 2007;115:3086-94. https://doi.org/10.1161/circulationaha.106.675041.\\u003c/li\\u003e\\n\\u003cli\\u003eLiesveld JL, Sharma N, Aljitawi OS. Stem cell homing: From physiology to therapeutics. Stem Cells 2020;38:1241-53. https://doi.org/10.1002/stem.3242.\\u003c/li\\u003e\\n\\u003cli\\u003eShirai T, Hanakita H, Uemichi K, Takemasa T. Effect of the order of concurrent training combined with resistance and high‐intensity interval exercise on mTOR signaling and glycolytic metabolism in mouse skeletal muscle. Physiological reports 2021;9:e14770. https://doi.org/10.14814/phy2.14770.\\u003c/li\\u003e\\n\\u003cli\\u003eKroepfl JM, Pekovits K, Stelzer I, et al. Exercise increases the frequency of circulating hematopoietic progenitor cells, but reduces hematopoietic colony-forming capacity. Stem cells and development 2012;21:2915-25. https://doi.org/10.1089/scd.2012.0017.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Epinephrine, Norepinephrine, Apheresis products, CD34+ cells, Mononuclear cells\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7178782/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7178782/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003ePurpose: \\u003c/strong\\u003eHematopoietic stem cells (HSCs) released from the bone marrow through mobilization have been used as a convenient source for Hematopoietic stem cell transplantation (HSCT). Exercise can mobilize HSCs into circulation in an intensity-dependent manner. Therefore, this study examined the effects of high-intensity interval exercise (HIIE) performed prior to HSCT on HSCs mobilization in autologous bone marrow transplant patients.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e: Twenty patients were divided into two groups. To determine peak power, patients in the exercise group performed a graded exercise test. After receiving the granulocyte-colony stimulating factor, they performed a HIIE protocol included 12 × 1-min effort at 100% peak power followed by 1-min active recovery at 20% of peak power. Blood samples were taken before and immediately after exercise and analyzed for catecholamine and CD34\\u003csup\\u003e+\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults\\u003c/strong\\u003e: Data analyses revealed significant increase (P\\u0026lt;0.05) in epinephrine, norepinephrine, and CD34\\u003csup\\u003e+\\u003c/sup\\u003e after exercise compare to control group. In addition, there was a positive correlation between epinephrine and CD34\\u003csup\\u003e+ \\u003c/sup\\u003eafter exercise in HIIE group. CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells, and mononuclear cells, were not significantly different between two groups (p\\u0026gt;0.05).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions\\u003c/strong\\u003e: It is concluded that HIIE is capable of mobilizing HSCs through increasing epinephrine. However, the increased catecholamine and CD34\\u003csup\\u003e+\\u003c/sup\\u003e cells after HIIE did not affect the apheresis products, possibly due to HSCs time courses and homing.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Hematopoietic stem cell mobilization folowing high-intensity interval exercise in cancer patients undergoing bone marrow transplantation : A clinical randomized trial \",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-11-01 11:47:28\",\"doi\":\"10.21203/rs.3.rs-7178782/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"37f4abcb-4a8a-4a40-aa93-ca360cabbf08\",\"owner\":[],\"postedDate\":\"November 1st, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-11-11T14:08:08+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-11-01 11:47:28\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7178782\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7178782\",\"identity\":\"rs-7178782\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}