{"paper_id":"15ac210c-008d-4be7-8e11-ea8b07810400","body_text":"Abstract\nObjective\nMenstrual 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.\nMethods\nE-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.\nResults\nApoptosis 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.\nConclusion\nIn 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.\nSimilar content being viewed by others\nReferences\nSmolarz B, Szyłło K, Romanowicz H. Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). Int J Mol Sci, 2021,22(19):1–29\nMoghaddam 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\nBonavina G, Taylor HS. Endometriosis-associated infertility: From pathophysiology to tailored treatment. Front Endocrinol, 2022,13:1–27\nBianco P. “Mesenchymal” stem cells. Annu Rev Cell Dev Biol, 2014,30:677–704\nBarry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol, 2004,36(4):568–584\nLee OK, Kuo TK, Chen WM, et al. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood, 2004,103(5):1669–1675\nZuk 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\nAnker 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\nKörbling 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\nCui 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\nMeng X, Elchim T, Zhong J, et al. Endometrial regenerative cells: a novel stem cell population. J Transl Med, 2007,5(57):1–10\nKhoury 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\nAna 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\nSundaram K, Miller DP, Kumar A, et al. Plant-Derived Exosomal Nanoparticles Inhibit Pathogenicity of Porphyromonas gingivalis. iScience, 2019,21:308–327\nDoyle LM, Wang MZ. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 2019,8(7):1–24\nBidarimath 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\nHuang-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\nAlfieri M, Leone A, Ambrosone A. Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine. Pharmaceutics, 2021,13(498):1–21\nBerger 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\nChen X, Liu B, Li X, et al. Identification of anti-inflammatory vesicle-like nanoparticles in honey. J Extracell Vesicles, 2021,10(4):e12069\nChen 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\nSriwastva 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\nJu 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\nKim DK, Rhee WJ. Antioxidative Effects of Carrot-Derived Nanovesicles in Cardiomyoblast and Neuroblastoma Cells. Pharmaceutics, 2021,13(8):1–12\nKim 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\nYang 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\nZhang 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\nKim 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\nVader P, Mol EA, Pasterkamp G, et al. Extracellular vesicles for drug delivery. Adv Drug Deliv Rev, 2016,106:148–156\nYang 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\nKooijmans SA, Vader P, Dommelen SM, et al. Exosome mimetics: a novel class of drug delivery systems. Int J Nanomedicine, 2012,16(7):1525–1541\nLobb 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\nBos-Mikich A, Oliveira R, Frantz N. Platelet-rich plasma therapy and reproductive medicine. J Assist Reprod Genet, 2018,35(5):753–756\nDawood 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\nZemljic M, Pejkovic B, Krajnc I, et al. Modern stem cell therapy: approach to disease. Wien Klin Wochenschr, 2015,127(5):199–203\nZhang 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\nZhao 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\nDodd 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\nLidani KCF, Andrade FA, Bavia L, et al. Chagas Disease: From Discovery to a Worldwide Health Problem. Front Public Health, 2019,7:1–13\nHao S, Yang H, Hu J, et al. Bioactive compounds and biological functions of medicinal plant-derived extracellular vesicles. Pharmacol Res, 2024,200:1–12\nAlzahrani 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\nLian 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\nTahir 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\nLiu 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\nCakir 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\nFunk 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\nEl-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\nFilho 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\nSahraei 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\nZhang 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\nVetvicka 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\nSikora 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\nAugoulea 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\nFreger 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\nHajazimian S, Maleki M, Mehrabad SD, et al. Human Wharton’s jelly stem cells inhibit endometriosis through apoptosis induction. Reproduction, 2020,159(5):549–558\nYerlikaya 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\nOliveira 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\nDavoodi 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\nLuddi 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\nVelarde 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\nSzymański M, Bonowicz K, Antosik P, et al. Role of Cyclins and Cytoskeletal Proteins in Endometriosis: Insights into Pathophysiology. Cancers, 2024,16(4):836–861\nKobayashi H, Taniguchi F, Azuma Y, et al. Fetal programming theory: implication for the understanding of endometriosis. Hum Immunol, 2014,75(3):208–217\nKaponis A, Taniguchi F, Azuma Y, et al. Current treatment of endometrioma. Obstet Gynecol Surv, 2015,70(3):183–195\nCalcagno 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\nHoushdaran 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\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nThe authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.\nRights and permissions\nAbout this article\nCite this article\nAbabzadeh, 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\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s11596-024-2939-2","source_license":"public-domain-us","license_restricted":false}