{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:13:49Z","timestamp":1777011229727,"version":"3.51.4"},"reference-count":85,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dual-double stem cell therapy, which integrates mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), represents a cutting-edge approach in regenerative medicine, particularly for conditions such as ovarian decline, premature ovarian insufficiency (POI), and induced ovarian failure. This therapy leverages the unique properties of MSCs and HSCs, enhancing tissue repair, immune modulation, and overall regenerative outcomes. MSCs, known for their ability to differentiate into various cell types, provide a supportive microenvironment and secrete bioactive molecules that promote angiogenesis and reduce inflammation. HSCs, crucial for hematopoiesis and immune function, further enhance this environment by supporting hematopoietic processes and immune regulation. Clinical evidence increasingly supports the effectiveness of stem cell therapy in ovarian regeneration. Studies have demonstrated improved folliculogenesis, normalization of hormone profiles, and successful pregnancies in patients with POI. Furthermore, recent clinical trials in various medical fields underline the superior potential of dual-double therapy compared to monotherapies involving MSCs or HSCs alone, enhancing tissue repair and functional outcomes. However, despite these benefits, the therapy presents risks that require careful consideration. For autologous MSC therapy involving expanded cell populations, risks include tumorigenic potential, with evidence of sarcoma formation in certain cases of cultured MSCs. In contrast, autologous non-expanded MSC and HSC therapies may be limited by low cell yields, potentially compromising therapeutic efficacy. Additionally, non-expanded HSC therapy poses risks of insufficient cell numbers for successful engraftment and delayed immune reconstitution. These considerations underscore the importance of quality control and rigorous screening to optimize safety and efficacy. This article explores the mechanisms of action, clinical applications, and potential complications of dual-double stem cell therapy, underscoring the need for continued research and optimized protocols to enhance safety and outcomes in ovarian insufficiency and related conditions, offering new hope for affected women.<\/jats:p>","DOI":"10.3390\/ijms26010069","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T19:29:52Z","timestamp":1735154992000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dual-Double Stem Cell Ovarian Therapy: A Comprehensive Approach in Regenerative Medicine"],"prefix":"10.3390","volume":"26","author":[{"given":"Aleksandar","family":"Ljubi\u0107","sequence":"first","affiliation":[{"name":"Pronatal Hospital, 11000 Belgrade, Serbia"},{"name":"Academy of Sciences and Arts of Bosnia and Herzegovina, 71000 Sarajevo, Bosnia and Herzegovina"},{"name":"Medigroup Health System, Dubrovnik International University, 20000 Dubrovnik, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Dini\u0107","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Apheresis, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dajana","family":"\u0160vraka","sequence":"additional","affiliation":[{"name":"Pronatal Hospital, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Vujovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Endocrinology, Diabetes and Diseases of National Center for Infertility and Endocrinology of Gender, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.molmed.2010.02.005","article-title":"Mesenchymal stem cell therapy: Two steps forward, one step back","volume":"16","author":"Ankrum","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nri2395","article-title":"Mesenchymal stem cells in health and disease","volume":"8","author":"Uccelli","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1161\/CIRCRESAHA.108.176826","article-title":"Paracrine mechanisms in adult stem cell signaling and therapy","volume":"103","author":"Gnecchi","year":"2008","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vizoso, F.J., Eiro, N., Cid, S., Schneider, J., and Perez-Fernandez, R. (2017). Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091852"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1053\/joca.2001.0504","article-title":"Human Autologous Culture Expanded Bone Marrow Mesenchymal Cell Transplantation for Repair of Cartilage Defects in Osteoarthritic Knees","volume":"10","author":"Wakitani","year":"2002","journal-title":"Osteoarthr. Cartil."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3464","DOI":"10.1002\/art.11365","article-title":"Stem Cell Therapy in a Caprine Model of Osteoarthritis","volume":"48","author":"Murphy","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_7","first-page":"648","article-title":"Cardiopoietic Cell Therapy for Advanced Ischemic Heart Failure: Results at 39 Weeks of the Randomized, Double-Blind, Sham-Controlled CHART-1 Clinical Trial","volume":"38","author":"Bartunek","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.imlet.2015.08.007","article-title":"Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection","volume":"168","author":"Laroni","year":"2015","journal-title":"Immunol. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1007\/s00415-020-10138-5","article-title":"Mesenchymal stem cell therapy for ischemic stroke: A look into treatment mechanism and therapeutic potential","volume":"268","author":"Li","year":"2021","journal-title":"J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Quertainmont, R., Cantinieaux, D., Botman, O., Sid, S., Schoenen, J., and Franzen, R. (2012). Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039500"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cell.2008.01.025","article-title":"Hematopoiesis: An evolving paradigm for stem cell biology","volume":"132","author":"Orkin","year":"2008","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0092-8674(00)81692-X","article-title":"Stem cells: Units of development, units of regeneration, and units in evolution","volume":"100","author":"Weissman","year":"2000","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMra052638","article-title":"Hematopoietic stem-cell transplantation","volume":"354","author":"Copelan","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1056\/NEJM199608083350601","article-title":"Bone marrow transplantation for sickle cell disease","volume":"335","author":"Walters","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3324\/haematol.2013.099747","article-title":"Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: Indications and management recommendations from an international expert panel","volume":"99","author":"Angelucci","year":"2014","journal-title":"Haematologica"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/jcb.20886","article-title":"Mesenchymal stem cells as trophic mediators","volume":"98","author":"Caplan","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1089\/107632701300062859","article-title":"Multilineage cells from human adipose tissue: Implications for cell-based therapies","volume":"7","author":"Zuk","year":"2001","journal-title":"Tissue Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1161\/01.RES.0000265074.83288.09","article-title":"Adipose-derived stem cells for regenerative medicine","volume":"100","author":"Gimble","year":"2007","journal-title":"Circ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1161\/01.CIR.0000121425.42966.F1","article-title":"Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells","volume":"109","author":"Rehman","year":"2004","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1634\/stemcells.2004-0013","article-title":"Mesenchymal stem cells in the Wharton\u2019s jelly of the human umbilical cord","volume":"22","author":"Wang","year":"2004","journal-title":"Stem Cells"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1634\/stemcells.2005-0330","article-title":"Human umbilical cord matrix stem cells: Preliminary characterization and effect of transplantation in a rodent model of Parkinson\u2019s disease","volume":"24","author":"Weiss","year":"2006","journal-title":"Stem Cells"},{"key":"ref_22","first-page":"243","article-title":"Effects of human umbilical cord-derived mesenchymal stem cells on premature ovarian insufficiency in mice","volume":"8","author":"Li","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_23","first-page":"117","article-title":"Transplantation of umbilical cord mesenchymal stem cells on collagen scaffolds improves ovarian function in rats with premature ovarian insufficiency","volume":"9","author":"Ding","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1200\/JCO.2006.10.3028","article-title":"Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure","volume":"25","author":"Lee","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.fertnstert.2018.01.004","article-title":"Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion","volume":"109","author":"Herraiz","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/labinvest.2012.167","article-title":"The restorative effect of adipose-derived mesenchymal stem cells on damaged ovarian function","volume":"93","author":"Takehara","year":"2013","journal-title":"Lab. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-019-1315-9","article-title":"Transplantation of human menstrual blood-derived stem cells restores ovarian function in a premature ovarian failure mouse model","volume":"10","author":"Liu","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/scrt231","article-title":"Adipose-derived stem cells improved mouse ovary function after chemotherapy-induced ovary failure","volume":"4","author":"Sun","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1186\/s13287-021-02529-w","article-title":"Transplantation of human umbilical cord mesenchymal stem cells to treat premature ovarian failure","volume":"12","author":"Yousefi","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, S., Yu, L., Sun, M., Mu, S., Wang, C., Wang, D., and Zhao, S. (2013). The therapeutic potential of umbilical cord mesenchymal stem cells in mice premature ovarian failure. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/690491"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Guo, C., Ma, Y., Situ, Y., Liu, L., Luo, G., Li, H., Ma, W., Sun, L., Wang, W., and Weng, Q. (2023). Mesenchymal stem cells therapy improves ovarian function in premature ovarian failure: A systematic review and meta-analysis based on preclinical studies. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1165574"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"310","DOI":"10.18203\/2320-1770.ijrcog20230114","article-title":"Effects of autologous stem cell therapy for fertility enhancement among women with premature ovarian insufficiency","volume":"12","author":"Banu","year":"2023","journal-title":"Int. J. Reprod. Contracept. Obstet. Gynecol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14553","DOI":"10.18632\/aging.205400","article-title":"Systemic changes induced by autologous stem cell ovarian transplant in plasma proteome of women with impaired ovarian reserves","volume":"15","author":"Buigues","year":"2023","journal-title":"Aging"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Baglio, S.R., Pegtel, D.M., and Baldini, N. (2012). Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Front. Physiol., 3.","DOI":"10.3389\/fphys.2012.00359"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00404-023-07062-0","article-title":"Stem cell therapy for premature ovarian insufficiency: A systematic review and meta-analysis of animal and clinical studies","volume":"309","author":"Hu","year":"2024","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/mt.2015.44","article-title":"Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications","volume":"23","author":"Rani","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5029619","DOI":"10.1155\/2016\/5029619","article-title":"Towards therapeutic delivery of extracellular vesicles: Strategies for in vivo tracking and biodistribution analysis","volume":"2016","author":"Baldari","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.stem.2009.02.001","article-title":"Mesenchymal stem cell homing: The devil is in the details","volume":"4","author":"Karp","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_39","unstructured":"Lin, H., Chen, X., and Wang, X. (2020). Bioactive factors in MSC-CM and ovarian tissue repair. Int. J. Mol. Sci., 21."},{"key":"ref_40","first-page":"45","article-title":"Mechanisms of MSC therapy in ovarian regeneration","volume":"14","author":"Wang","year":"2021","journal-title":"J. Ovarian Res."},{"key":"ref_41","unstructured":"Luo, Y., Shi, H., and Li, M. (2022). IGF-1 in MSC-mediated follicular preservation. Biochim. Biophys. Acta BBA Mol. Cell Res., 1869."},{"key":"ref_42","first-page":"1365","article-title":"ECM remodeling in ovarian rejuvenation using MSCs","volume":"17","author":"Liang","year":"2021","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_43","first-page":"1540","article-title":"The anti-inflammatory properties of adipose-derived MSCs in ovarian therapy","volume":"28","author":"Li","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_44","unstructured":"Sun, X., Li, H., and Zhang, J. (2023). Matrix metalloproteinases in UCMSCs for ovarian function. Front. Cell Dev. Biol., 11."},{"key":"ref_45","first-page":"55","article-title":"The role of UCMSCs in hormone regulation and ECM remodeling","volume":"390","author":"Huang","year":"2022","journal-title":"Cell Tissue Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/s41409-022-01792-6","article-title":"The effect of hematopoietic stem cell transplantation on fertility and strategies for improvement","volume":"57","author":"Silva","year":"2022","journal-title":"Bone Marrow Transplant."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1080\/09513590.2016.1230193","article-title":"Ovarian insufficiency following allogeneic hematopoietic stem cell transplantation","volume":"33","author":"Kawano","year":"2017","journal-title":"Gynecol. Endocrinol."},{"key":"ref_48","first-page":"e58195","article-title":"Long-Term Ovarian Function Assessment After Haematopoietic Stem Cell Transplantation in Female Sickle Cell Anaemia Survivors","volume":"16","author":"Olowoselu","year":"2024","journal-title":"Cureus"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.fertnstert.2018.04.025","article-title":"Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders","volume":"110","author":"Herraiz","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.rbmo.2022.12.011","article-title":"Ovarian rescue in women with premature ovarian insufficiency: Facts and fiction","volume":"46","author":"Pellicer","year":"2023","journal-title":"Reprod. Biomed. Online"},{"key":"ref_51","first-page":"178","article-title":"Influence of Autologous In Vitro Activation of Ovaries by Stem Cells and Growth Factors on Endocrine and Reproductive Function of Patients with Ovarian Insufficiency-A Clinical Trial Study","volume":"15","year":"2021","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_52","first-page":"118","article-title":"Ovarian tissue microfragmentation and exposure to autologous growth factors in vitro and reproductive outcome after orthotopic retransplantation","volume":"16","author":"Katica","year":"2022","journal-title":"Obstet. Gynecol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.fertnstert.2011.03.108","article-title":"Clinical and biologic evaluation of ovarian function in women treated by bone marrow transplantation for various indications during childhood or adolescence","volume":"96","author":"Jadoul","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0140-6736(01)05482-4","article-title":"Late Effects Working Party of the European Group for Blood and Marrow Transplantation Pregnancy outcomes after peripheral blood or bone marrow transplantation: A retrospective survey","volume":"358","author":"Salooja","year":"2001","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6487","DOI":"10.7150\/thno.102641","article-title":"Engineering mesenchymal stem cells for premature ovarian failure: Overcoming challenges and innovating therapeutic strategies","volume":"14","author":"Yuan","year":"2024","journal-title":"Theranostics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101804","DOI":"10.1016\/j.jcot.2022.101804","article-title":"The promising role of autologous and allogeneic mesenchymal stromal cells in managing knee osteoarthritis. What is beyond Mesenchymal stromal cells?","volume":"26","author":"Pandey","year":"2022","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1002\/jcb.26637","article-title":"Mechanistic effects of mesenchymal and hematopoietic stem cells: New therapeutic targets in myocardial infarction","volume":"119","author":"Shafei","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1161\/CIRCRESAHA.116.304346","article-title":"ACCRUE Investigators Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data","volume":"116","author":"Wojakowski","year":"2015","journal-title":"Circ. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1161\/CIRCRESAHA.119.314951","article-title":"Phase 3 DREAM-HF Trial of Mesenchymal Precursor Cells in Chronic Heart Failure","volume":"125","author":"Borow","year":"2019","journal-title":"Circ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Soares, M.B.P., Gon\u00e7alves, R.G.J., Vasques, J.F., da Silva-Junior, A.J., Gubert, F., Santos, G.C., de Santana, T.A., Almeida Sampaio, G.L., Silva, D.N., and Dominici, M. (2022). Current Status of Mesenchymal Stem\/Stromal Cells for Treatment of Neurological Diseases. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.883378"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11275","DOI":"10.3390\/ijms150711275","article-title":"Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat","volume":"15","author":"LaBagnara","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ercelen, N., Karasu, N., Kahyaoglu, B., Cerezci, O., Akduman, R.C., Ercelen, D., Erturk, G., Gulay, G., Alpaydin, N., and Boyraz, G. (2023). Clinical experience: Outcomes of mesenchymal stem cell transplantation in five stroke patients. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1051831"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5653\/cerm.2019.46.1.1","article-title":"Mesenchymal stem cells for restoration of ovarian function","volume":"46","author":"Yoon","year":"2019","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.3727\/096368913X667709","article-title":"Paracrine mechanisms of mesenchymal stem cell-based therapy: Current status and perspectives","volume":"23","author":"Liang","year":"2014","journal-title":"Cell Transplant."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s13287-021-02212-0","article-title":"Human mesenchymal stem cell treatment of premature ovarian failure: New challenges and opportunities","volume":"12","author":"Fu","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_66","first-page":"302","article-title":"Transplantation of umbilical cord-derived mesenchymal stem cells on a collagen scaffold improves ovarian function in a premature ovarian failure model of mice. In vitro cellular & developmental biology","volume":"55","author":"Yang","year":"2019","journal-title":"Animal"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1007\/s43032-021-00499-1","article-title":"Human Umbilical Cord Mesenchymal Stem Cells Improve Ovarian Function in Chemotherapy-Induced Premature Ovarian Failure Mice Through Inhibiting Apoptosis and Inflammation via a Paracrine Mechanism","volume":"28","author":"Deng","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Liao, Z., Liu, C., Wang, L., Sui, C., and Zhang, H. (2021). Therapeutic Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Female Reproductive Diseases. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.665645"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13287-023-03631-x","article-title":"Cellular and molecular mechanisms of highly active mesenchymal stem cells in the treatment of senescence of rhesus monkey ovary","volume":"15","author":"Wang","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.immuni.2006.10.016","article-title":"Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches","volume":"25","author":"Sugiyama","year":"2006","journal-title":"Immunity"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.it.2011.03.009","article-title":"Control of hematopoietic stem cells by the bone marrow stromal niche: The role of reticular cells","volume":"32","author":"Nagasawa","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.bbrc.2012.01.150","article-title":"Activated T-cells and pro-inflammatory cytokines differentially regulate prostaglandin E2 secretion by mesenchymal stem cells","volume":"419","author":"Hegyi","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.imlet.2007.04.001","article-title":"IFN-\u03b3 and TNF-\u03b1 differentially regulate immunomodulation by murine mesenchymal stem cells","volume":"110","author":"English","year":"2007","journal-title":"Immunol. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13287-022-02724-3","article-title":"Mesenchymal stem cells combined with autocrosslinked hyaluronic acid improve mouse ovarian function by activating the PI3K-AKT pathway in a paracrine manner","volume":"13","author":"Jiao","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13287-021-02275-z","article-title":"Human placental mesenchymal stem cells ameliorate chemotherapy-induced damage in the testis by reducing apoptosis\/oxidative stress and promoting autophagy","volume":"12","author":"Lu","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chase, L., and Vemuri, M. (2013). Mesenchymal Stem Cell Exosomes: The Future MSC-Based Therapy?. Mesenchymal Stem Cell Therapy. Stem Cell Biology and Regenerative Medicine, Humana Press.","DOI":"10.1007\/978-1-62703-200-1"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0897.2011.01069.x","article-title":"Immunomodulatory properties of mesenchymal stem cells: Cytokines and factors","volume":"67","author":"Soleymaninejadian","year":"2012","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Thompson, M., Mei, S.H.J., Wolfe, D., Champagne, J., Fergusson, D., Stewart, D.J., and Keating, A. (2020). Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis. EBioMedicine, 59.","DOI":"10.1016\/j.eclinm.2019.100249"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1634\/stemcells.2005-0620","article-title":"Sarcoma derived from cultured mesenchymal stem cells","volume":"25","author":"Tolar","year":"2007","journal-title":"Stem Cells"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.1158\/0008-5472.CAN-09-4640","article-title":"Deficiency in p53 but not retinoblastoma induces the transformation of mesenchymal stem cells in vitro and initiates leiomyosarcoma in vivo","volume":"70","author":"Rubio","year":"2010","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/path.2603","article-title":"Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2","volume":"219","author":"Mohseny","year":"2009","journal-title":"J. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1016\/j.bbmt.2015.07.032","article-title":"Indications for autologous and allogeneic hematopoietic cell transplantation: Guidelines from the American Society for Blood and Marrow Transplantation","volume":"21","author":"Majhail","year":"2015","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1056\/NEJMp078166","article-title":"Hematopoietic-cell transplantation at 50","volume":"357","author":"Appelbaum","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/scrt217","article-title":"Production of mesenchymal stromal\/stem cells according to good manufacturing practices: A review","volume":"4","author":"Gadelorge","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Carreras, E., Dufour, C., Mohty, M., and Kr\u00f6ger, N. (2019). The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies, Springer Open.","DOI":"10.1007\/978-3-030-02278-5"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/69\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:59:55Z","timestamp":1760115595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/69"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,25]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26010069"],"URL":"https:\/\/doi.org\/10.3390\/ijms26010069","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,25]]}}}