Effects of Exosomes from Menstrual Blood-derived Stem Cells and Ginger on Endometriotic Stem Cells

Current medical science · 2024 · vol. 44(6) , pp. 1293–1302 · doi:10.1007/s11596-024-2939-2 · PMID:39565506
other OA: closed public-domain-us
Full text JSON View on PubMed View at publisher
AI-generated summary by claude@2026-06, 2026-06-13

Exosomes from menstrual blood stem cells and ginger root increased apoptosis and modulated gene expression in endometriotic stem cells, with ginger exosomes showing promise for clinical applications.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-13 · read from full text

The study compared the effects of exosomes derived from menstrual blood-derived stem cells from endometriosis patients (C-exos) versus ginger roots (P-exos) on endometriotic menstrual blood-derived stem cells (E-MenSCs), using third-passage cells treated for 72 hours at doses selected by MTT, followed by annexin V/PI apoptosis assays and real-time PCR for inflammatory, cell cycle, steroid, migration/invasion, and apoptosis-related genes. Both C-exos and P-exos increased apoptosis, while P-exos specifically lowered IL-6 and IL-1β relative to untreated E-MenSCs and reduced IL-8, NF-κB, COX-2, MMP-9, VEGF, and the BAX/BCL2 ratio compared with E-MenSCs. The authors’ limitation, stated via the experimental design, is that this work is confined to in vitro treatment of E-MenSCs rather than demonstrating effects in an in vivo or clinical setting. This paper is centrally about endometriosis — it tests ginger- and menstrual-stem-cell-derived exosomes on endometriotic stem cells to modulate inflammatory, angiogenic, migratory, and apoptosis pathways.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

OBJECTIVE: Menstrual blood-derived stem cells from endometriosis patients (E-MenSCs) have different gene expression patterns than those from healthy nonendometriotic females (NE-MenSCs). Exosomes extracted from mesenchymal stem cells and plants are considered for the treatment of various diseases. This study aimed to compare the effects of exosomes derived from NE-MenSCs (C-exos) and those from the roots of ginger (P-exos) on E-MenSCs. METHODS: E-MenSCs at the third passage were used, and after evaluating the effective dosage with MTT, C-exos (200 µg/mL) or P-exos (100 µg/mL) were added to treat them. Following a 72-h incubation, the cells were analyzed with annexin V/PI test to evaluate the apoptosis rate. Also, genes related to inflammation (IL-6, IL-8, IL-1β, NF-κB, COX2), cell cycle (Cyclin D1), the steroid pathway (ESR1), migration and invasion (MMP-2, MMP-9, VEGF), and the apoptosis pathway (BAX, BCL2) were detected by real-time PCR. RESULTS: Apoptosis was increased in both the P- and C-exos groups. The expression levels of IL-6 and IL-1β were significantly lower in the P-exos group than in the E-MenSCs group. The expression levels of IL-8, NF-κB, COX-2, and MMP-9 were significantly decreased in both the P-exos group and the C-exos group. The expression level of VEGF was significantly lower in the P-exos group than in the E-MenSCs group. The BAX/BCL2 ratio was much lower in the P-exos group than in the E-MenSCs group. CONCLUSION: In this study, we established the feasibility of using a novel natural nontoxic material to target endometriotic mesenchymal stem cells to modify their gene expression and function toward healthy cells. Both C-exos and P-exos showed positive effects on the gene expression and function of endometriotic cells. Considering that plant exosomes are easier to access and less expensive, they can be considered for clinical use in improving the symptoms of endometriosis patients.
Full text 13,802 characters · extracted from oa-doi-fallback · 5 sections · click to expand

Abstract

Objective Menstrual blood-derived stem cells from endometriosis patients (E-MenSCs) have different gene expression patterns than those from healthy nonendometriotic females (NE-MenSCs). Exosomes extracted from mesenchymal stem cells and plants are considered for the treatment of various diseases. This study aimed to compare the effects of exosomes derived from NE-MenSCs (C-exos) and those from the roots of ginger (P-exos) on E-MenSCs.

Methods

E-MenSCs at the third passage were used, and after evaluating the effective dosage with MTT, C-exos (200 µg/mL) or P-exos (100 µg/mL) were added to treat them. Following a 72-h incubation, the cells were analyzed with annexin V/PI test to evaluate the apoptosis rate. Also, genes related to inflammation (IL-6, IL-8, IL-1β, NF-κB, COX2), cell cycle (Cyclin D1), the steroid pathway (ESR1), migration and invasion (MMP-2, MMP-9, VEGF), and the apoptosis pathway (BAX, BCL2) were detected by real-time PCR.

Results

Apoptosis was increased in both the P- and C-exos groups. The expression levels of IL-6 and IL-1β were significantly lower in the P-exos group than in the E-MenSCs group. The expression levels of IL-8, NF-κB, COX-2, and MMP-9 were significantly decreased in both the P-exos group and the C-exos group. The expression level of VEGF was significantly lower in the P-exos group than in the E-MenSCs group. The BAX/BCL2 ratio was much lower in the P-exos group than in the E-MenSCs group.

Conclusion

In this study, we established the feasibility of using a novel natural nontoxic material to target endometriotic mesenchymal stem cells to modify their gene expression and function toward healthy cells. Both C-exos and P-exos showed positive effects on the gene expression and function of endometriotic cells. Considering that plant exosomes are easier to access and less expensive, they can be considered for clinical use in improving the symptoms of endometriosis patients. Similar content being viewed by others

References

Smolarz B, Szyłło K, Romanowicz H. Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). Int J Mol Sci, 2021,22(19):1–29 Moghaddam MZ, Ansariniya H, Seifati SM, et al. Immunopathogenesis of endometriosis: An overview of the role of innate and adaptive immune cells and their mediators. Am J Reprod Immunol, 2022,87(5):e13537 Bonavina G, Taylor HS. Endometriosis-associated infertility: From pathophysiology to tailored treatment. Front Endocrinol, 2022,13:1–27 Bianco P. “Mesenchymal” stem cells. Annu Rev Cell Dev Biol, 2014,30:677–704 Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol, 2004,36(4):568–584 Lee OK, Kuo TK, Chen WM, et al. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood, 2004,103(5):1669–1675 Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell, 2002,13(12):4279–4295 Anker PS, Scherjon SA, Kleijburg-van der Keur C, et al. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells, 2004,22(7):1338–1345 Körbling M, Anderlini P. Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood, 2001,98(10):2900–2908 Cui CH, Uyama T, Miyado K, et al. Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation. Mol Biol Cell, 2007,18(5):1586–1594 Meng X, Elchim T, Zhong J, et al. Endometrial regenerative cells: a novel stem cell population. J Transl Med, 2007,5(57):1–10 Khoury M, Alcayaga-Miranda F, E Illanes S, et al. The promising potential of menstrual stem cells for antenatal diagnosis and cell therapy. Front Immunol, 2014,5(205):1–8 Ana ID, Barlian A, Hidajah AC, et al. Challenges and strategy in treatment with exosomes for cell-free-based tissue engineering in dentistry. Future Sci OA, 2021,7(10):1–21 Sundaram K, Miller DP, Kumar A, et al. Plant-Derived Exosomal Nanoparticles Inhibit Pathogenicity of Porphyromonas gingivalis. iScience, 2019,21:308–327 Doyle LM, Wang MZ. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 2019,8(7):1–24 Bidarimath M, Khalaj K, Kridli RT, et al. Extracellular vesicle mediated intercellular communication at the porcine maternal-fetal interface: A new paradigm for conceptus-endometrial cross-talk. Sci Rep, 2017,7:1–14 Huang-Doran I, Zhang CY, Vidal-Puig A. Extracellular Vesicles: Novel Mediators of Cell Communication In Metabolic Disease. Trends Endocrinol Metab, 2017,28(1):3–18 Alfieri M, Leone A, Ambrosone A. Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine. Pharmaceutics, 2021,13(498):1–21 Berger E, Colosetti P, Jalabert A, et al. Use of Nanovesicles from Orange Juice to Reverse Diet-Induced Gut Modifications in Diet-Induced Obese Mice. Mol Ther Methods Clin Dev, 2020,18:880–892 Chen X, Liu B, Li X, et al. Identification of anti-inflammatory vesicle-like nanoparticles in honey. J Extracell Vesicles, 2021,10(4):e12069 Chen YS, Lin EY, Chiou TW, et al. Exosomes in clinical trial and their production in compliance with good manufacturing practice. Ci Ji Yi Xue Za Zhi (Chinese), 2020,32(2):113–120 Sriwastva MK, Deng ZB, Wang B, et al. Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway. EMBO Rep, 2022,23(3):e53365 Ju S, Mu J, Dokland T, et al. Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Mol Ther, 2013,21(7):1345–1357 Kim DK, Rhee WJ. Antioxidative Effects of Carrot-Derived Nanovesicles in Cardiomyoblast and Neuroblastoma Cells. Pharmaceutics, 2021,13(8):1–12 Kim K, Jung JH, Yoo HJ, et al. Anti-Metastatic Effects of Plant Sap-Derived Extracellular Vesicles in a 3D Microfluidic Cancer Metastasis Model. J Funct Biomater, 2020,11(49):1–13 Yang M, Liu X, Luo Q, et al. An efficient method to isolate lemon derived extracellular vesicles for gastric cancer therapy. J Nanobiotechnology, 2020,18(100):1–12 Zhang M, Viennois E, Prasad M, et al. Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials, 2016,101:321–340 Kim J, Li S, Zhang S, et al. Plant-derived exosome-like nanoparticles and their therapeutic activities. Asian J Pharm Sci, 2022,17(1):53–69 Vader P, Mol EA, Pasterkamp G, et al. Extracellular vesicles for drug delivery. Adv Drug Deliv Rev, 2016,106:148–156 Yang C, Zhang M, Merlin D. Advances in plant-derived edible nanoparticle-based lipid nano-drug delivery systems as therapeutic nanomedicines. J Mater Chem B, 2018,6(9):1312–1321 Kooijmans SA, Vader P, Dommelen SM, et al. Exosome mimetics: a novel class of drug delivery systems. Int J Nanomedicine, 2012,16(7):1525–1541 Lobb RJ, Becker M, Wen SW, et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracell Vesicles, 2015,4(1):1–11 Bos-Mikich A, Oliveira R, Frantz N. Platelet-rich plasma therapy and reproductive medicine. J Assist Reprod Genet, 2018,35(5):753–756 Dawood AS, Salem HA. Current clinical applications of platelet-rich plasma in various gynecological disorders: An appraisal of theory and practice. Clin Exp Reprod Med, 2018,45(2):67–74 Zemljic M, Pejkovic B, Krajnc I, et al. Modern stem cell therapy: approach to disease. Wien Klin Wochenschr, 2015,127(5):199–203 Zhang S, Chuah SJ, Lai RC, et al. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials, 2018,156:16–27 Zhao Y, Jiang M, Wu Y, et al. Mitochondrial genomes of three kissing bugs (Reduviidae: Triatominae) and their phylogenetic implications. Int J Biol Macromol, 2019,134:36–42 Dodd RY, Groves JA, Townsend RL, et al. Impact of one-time testing for Trypanosoma cruzi antibodies among blood donors in the United States. Transfusion, 2019,59(3):1016–1023 Lidani KCF, Andrade FA, Bavia L, et al. Chagas Disease: From Discovery to a Worldwide Health Problem. Front Public Health, 2019,7:1–13 Hao S, Yang H, Hu J, et al. Bioactive compounds and biological functions of medicinal plant-derived extracellular vesicles. Pharmacol Res, 2024,200:1–12 Alzahrani FA, Imran Khan M, Kameli N, et al. Plant-Derived Extracellular Vesicles and Their Exciting Potential as the Future of Next-Generation Drug Delivery. Biomolecules, 2023,13(5):1–22 Lian MQ, Chng WH, Liang J, et al. Plant-derived extracellular vesicles: Recent advancements and current challenges on their use for biomedical applications. J Extracell Vesicles, 2022,11(12):e12283 Tahir AA, Abdul Sani NF, Murad NA, et al. Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells. Nutr J, 2015,14(31):1–10 Liu CM, Kao CL, Tseng YT, et al. Ginger phytochemicals inhibit cell growth and modulate drug resistance factors in docetaxel resistant prostate cancer cell. Molecules, 2017,22(9):1477–1486 Cakir U, Tayman C, Serkant U, et al. Ginger (Zingiber officinale Roscoe) for the treatment and prevention of necrotizing enterocolitis. J Ethnopharmacol, 2018,225:297–308 Funk JL, Frye JB, Oyarzo JN, et al. Anti-Inflammatory Effects of the Essential Oils of Ginger (Zingiber officinale Roscoe) in Experimental Rheumatoid Arthritis. Pharma Nutrition, 2016,4(3):123–131 El-Ashmawy NE, Khedr NF, El-Bahrawy HA, et al. Ginger extract adjuvant to doxorubicin in mammary carcinoma: study of some molecular mechanisms. Eur J Nutr, 2018,57(3):981–989 Filho JMdM, Neto JN, Sousa Gomes LMR, et al. Zingiber officinale Roscoe (Ginger) as a Complementary Option for Clinical Treatment of Endometriosis: An Experimental Study in Rats. J Med Food, 2020,24(4):342–347 Sahraei SS, Davoodi Asl F, Kalhor N, et al. A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women. Biomed Res Int, 2022,2022:1–11 Zhang W, Wang Y, Kong J, et al. Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy. Sci Rep, 2017,7(1):408–416 Vetvicka V, Lagana AS, Salmeri FM, et al. Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives. Arch Gynecol Obstet, 2016,294(5):897–904 Sikora J, Smycz-Kubańska M, Mielczarek-Palacz A, et al. Abnormal peritoneal regulation of chemokine activation—The role of IL-8 in pathogenesis of endometriosis. Am J Reprod Immunol, 2017,77(4):1–8 Augoulea A, Alexandrou A, Creatsa M, et al. Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress. Arch Gynecol Obstet, 2012,286(1):99–103 Freger S, Leonardi M, Foster WG. Exosomes and their cargo are important regulators of cell function in endometriosis. Reprod Biomed Online, 2021,43(3):370–378 Hajazimian S, Maleki M, Mehrabad SD, et al. Human Wharton’s jelly stem cells inhibit endometriosis through apoptosis induction. Reproduction, 2020,159(5):549–558 Yerlikaya G, Balendran S, Pröstling K, et al. Comprehensive study of angiogenic factors in women with endometriosis compared to women without endometriosis. Eur J Obstet Gynecol Reprod Biol, 2016,204:88–98 Oliveira FR, Cruz CD, Puerto D, et al. Stem cells: are they the answer to the puzzling etiology of endometriosis? Histol Histopathol, 2012,27(1):23–29 Davoodi Asl F, Sahraei SS, Kalhor N, et al. Promising effects of exosomes from menstrual blood-derived mesenchymal stem cells on endometriosis. Reprod Biol, 2023,23(3):1–13 Luddi A, Marrocco C, Governini L, et al. Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions. Int J Mol Sci, 2020,21(8):1–14 Velarde MC, Aghajanova L, Nezhat CR, et al. Increased mitogen-activated protein kinase kinase/extracellularly regulated kinase activity in human endometrial stromal fibroblasts of women with endometriosis reduces 3′,5′-cyclic adenosine 5′-monophosphate inhibition of cyclin D1. Endocrinology, 2009,150(10):4701–4712 Szymański M, Bonowicz K, Antosik P, et al. Role of Cyclins and Cytoskeletal Proteins in Endometriosis: Insights into Pathophysiology. Cancers, 2024,16(4):836–861 Kobayashi H, Taniguchi F, Azuma Y, et al. Fetal programming theory: implication for the understanding of endometriosis. Hum Immunol, 2014,75(3):208–217 Kaponis A, Taniguchi F, Azuma Y, et al. Current treatment of endometrioma. Obstet Gynecol Surv, 2015,70(3):183–195 Calcagno A, Grassi T, Mariuzzi L, et al. Expression patterns of Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors determined using an endometriosis tissue microarray model. Hum Reprod, 2011,26(10):2731–2741 Houshdaran S, Oke AB, Fung JC, et al. Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis. PLoS Genet, 2020,16(6):e1008601 Author information Authors and Affiliations Corresponding author Ethics declarations The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work. Rights and permissions About this article Cite this article Ababzadeh, S., Davoodi Asl, F., Fazaeli, H. et al. Effects of Exosomes from Menstrual Blood-derived Stem Cells and Ginger on Endometriotic Stem Cells. CURR MED SCI 44, 1293–1302 (2024). https://doi.org/10.1007/s11596-024-2939-2 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11596-024-2939-2

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis Apoptosis

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2024) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-08-11T06:11:44.160905+00:00
pubmed
last seen: 2026-08-11T06:09:21.122484+00:00
unpaywall
last seen: 2026-08-11T06:58:28.661508+00:00
License: public-domain-us · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine