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An update on stem cell therapy for Asherman syndrome

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Abstract

The current treatment for Asherman syndrome is limited and not very effective. The aim of this review is to summarize the most recent evidence for stem cells in the treatment of Asherman syndrome. The advent of stem cell therapy has propagated experimentation on mice and humans as a novel treatment. The consensus is that the regenerative capacity of stem cells has demonstrated improved outcomes in terms of fertility and fibrosis in both mice and humans with Asherman syndrome. Stem cells have effects on tissue repair by homing to the injured site, recruiting other cells by secreting chemokines, modulating the immune system, differentiating into other types of cells, proliferating into daughter cells, and potentially having antimicrobial activity. The studies reviewed examine different origins and administration modalities of stem cells. In preclinical models, therapeutic systemic injection of stem cells is more effective than direct intrauterine injection in regenerating the endometrium. In conjunction, bone marrow-derived stem cells have a stronger effect on uterine regeneration than uterine-derived stem cells, likely due to their broader differentiation potency. Clinical trials have demonstrated the initial safety and effectiveness profiles of menstrual, bone marrow, umbilical cord, and adipose tissue-derived stem cells in resumption of menstruation, fertility outcomes, and endometrial regeneration.

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References

  1. Soares SR, Barbosa dos Reis MM, Camargos AF. Diagnostic accuracy of sonohysterography, transvaginal sonography, and hysterosalpingography in patients with uterine cavity diseases. Fertil Steril. 2000;73(2):406–11.

    PubMed  CAS  Google Scholar 

  2. AAGL Practice report: practice guidelines for management of intrauterine synechiae. J Minim Invasive Gynecol. 2010;17(1):1–7.

  3. Hu J, Zeng B, Jiang X, Hu L, Meng Y, Zhu Y, et al. The expression of marker for endometrial stem cell and fibrosis was increased in intrauterine adhesious. Int J Clin Exp Pathol. 2015;8(2):1525–34.

    PubMed  PubMed Central  CAS  Google Scholar 

  4. Zhu Y, Hu J, Yu T, Ren Y, Hu L. High molecular weight hyaluronic acid inhibits fibrosis of endometrium. Med Sci Monit. 2016;22:3438–45.

    PubMed  PubMed Central  CAS  Google Scholar 

  5. Bai X, Liu J, Cao S, Wang L. Mechanisms of endometrial fibrosis and the potential application of stem cell therapy. Discov Med. 2019;27(150):267–79.

    PubMed  Google Scholar 

  6. Liu D, Ha C, Zhang X, Zhang Z, Liu P. Molecular implication of ADAM-15 and -17 in intrauterine adhesions. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):264–9.

    PubMed  CAS  Google Scholar 

  7. Farhi J, Bar-Hava I, Homburg R, Dicker D, Ben-Rafael Z. Induced regeneration of endometrium following curettage for abortion: a comparative study. Hum Reprod. 1993;8(7):1143–4.

    PubMed  CAS  Google Scholar 

  8. AAGL Elevating Gynecologic Surgery. AAGL practice report: practice guidelines on intrauterine adhesions developed in collaboration with the European Society of Gynaecological Endoscopy (ESGE). Gynecol Surg. 2017;14(1):6.

    PubMed Central  Google Scholar 

  9. Johary J, Xue M, Zhu X, Xu D, Velu PP. Efficacy of estrogen therapy in patients with intrauterine adhesions: systematic review. J Minim Invasive Gynecol. 2014;21(1):44–54.

    PubMed  Google Scholar 

  10. Guo J, Li TC, Liu Y, Xia E, Xiao Y, Zhou F, et al. A prospective, randomized, controlled trial comparing two doses of oestrogen therapy after hysteroscopic adhesiolysis to prevent intrauterine adhesion recurrence. Reprod BioMed Online. 2017;35(5):555–61.

    PubMed  CAS  Google Scholar 

  11. Myers EM, Hurst BS. Comprehensive management of severe Asherman syndrome and amenorrhea. Fertil Steril. 2012;97(1):160–4.

    PubMed  Google Scholar 

  12. Pabuccu R, Atay V, Orhon E, Urman B, Ergun A. Hysteroscopic treatment of intrauterine adhesions is safe and effective in the restoration of normal menstruation and fertility. Fertil Steril. 1997;68(6):1141–3.

    PubMed  CAS  Google Scholar 

  13. Conforti A, Alviggi C, Mollo A, De Placido G, Magos A. The management of Asherman syndrome: a review of literature. Reprod Biol Endocrinol. 2013;11:118. https://doi.org/10.1186/1477-7827-11-118.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Deans R, Abbott J. Review of intrauterine adhesions. J Minim Invasive Gynecol. 2010;17(5):555–69.

    PubMed  Google Scholar 

  15. Valle RF, Sciarra JJ. Intrauterine adhesions: hysteroscopic diagnosis, classification, treatment, and reproductive outcome. Am J Obstet Gynecol. 1988;158(6 Pt 1):1459–70.

    PubMed  CAS  Google Scholar 

  16. Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome--one century later. Fertil Steril. 2008;89(4):759–79.

    PubMed  Google Scholar 

  17. Gan L, Duan H, Sun FQ, Xu Q, Tang YQ, Wang S. Efficacy of freeze-dried amnion graft following hysteroscopic adhesiolysis of severe intrauterine adhesions. Int J Gynaecol Obstet. 2017;137(2):116–22.

    PubMed  Google Scholar 

  18. Robinson JK, Colimon LM, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome). Fertil Steril. 2008;90(2):409–14.

    PubMed  Google Scholar 

  19. Alawadhi F, Du H, Cakmak H, Taylor HS. Bone marrow-derived stem cell (BMDSC) transplantation improves fertility in a murine model of Asherman's syndrome. PLoS One. 2014;9(5):e96662.

    PubMed  PubMed Central  Google Scholar 

  20. Singh N, Mohanty S, Seth T, Shankar M, Bhaskaran S, Dharmendra S. Autologous stem cell transplantation in refractory Asherman's syndrome: a novel cell based therapy. J Hum Reprod Sci. 2014;7(2):93–8.

    PubMed  PubMed Central  Google Scholar 

  21. Santamaria X, Cabanillas S, Cervello I, Arbona C, Raga F, Ferro J, et al. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study. Hum Reprod. 2016;31(5):1087–96.

    PubMed  CAS  Google Scholar 

  22. Tan J, Li P, Wang Q, Li Y, Li X, Zhao D, et al. Autologous menstrual blood-derived stromal cells transplantation for severe Asherman's syndrome. Hum Reprod. 2016;31(12):2723–9.

    PubMed  Google Scholar 

  23. Nagori CB, Panchal SY, Patel H. Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman's syndrome. J Hum Reprod Sci. 2011;4(1):43–8.

    PubMed  PubMed Central  Google Scholar 

  24. Cervelló I, Gil-Sanchis C, Santamaria X, Cabanillas S, Diaz A, Faus A, et al. Human CD133(+) bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome. Fertil Steril. 2015;104(6):1552–60.e1–3.

    PubMed  Google Scholar 

  25. Gargett CE, Ye L. Endometrial reconstruction from stem cells. Fertil Steril. 2012;98(1):11–20.

    PubMed  Google Scholar 

  26. Gargett CE, Schwab KE, Deane JA. Endometrial stem/progenitor cells: the first 10 years. Hum Reprod Update. 2016;22(2):137–63.

    PubMed  CAS  Google Scholar 

  27. Santamaria X, Mas A, Cervelló TH, Simón C. Uterine stem cells: from basic research to advanced cell therapies. Hum Reprod Update. 2018;24(6):673–93.

    PubMed  CAS  Google Scholar 

  28. Deane JA, Gualano RC, Gargett CE. Regenerating endometrium from stem/progenitor cells: is it abnormal in endometriosis, Asherman's syndrome and infertility? Curr Opin Obstet Gynecol. 2013;25(3):193–200.

    PubMed  Google Scholar 

  29. Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004;292(1):81–5.

    PubMed  CAS  Google Scholar 

  30. Bianco P, Robey PG, Simmons PJ. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell. 2008;2(4):313–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Ye L, Mayberry R, Lo CY, Britt KL, Stanley EG, Elefanty AG, et al. Generation of human female reproductive tract epithelium from human embryonic stem cells. PLoS One. 2011;6(6):e21136.

    PubMed  PubMed Central  CAS  Google Scholar 

  32. Lee CL, Lam KK, Koistinen H, Seppala M, Kurpisz M, Fernandez N, et al. Glycodelin-a as a paracrine regulator in early pregnancy. J Reprod Immunol. 2011;90(1):29–34.

    PubMed  CAS  Google Scholar 

  33. Masuda H, Maruyama T, Gargett CE, Miyazaki K, Matsuzaki Y, Okano H, et al. Endometrial side population cells: potential adult stem/progenitor cells in endometrium. Biol Reprod. 2015;93(4):84.

    PubMed  Google Scholar 

  34. Mutlu L, Hufnagel D, Taylor HS. The endometrium as a source of mesenchymal stem cells for regenerative medicine. Biol Reprod. 2015;92(6):138.

    PubMed  PubMed Central  Google Scholar 

  35. Nguyen HPT, Xiao L, Deane JA, Tan KS, Cousins FL, Masuda H, et al. N-cadherin identifies human endometrial epithelial progenitor cells by in vitro stem cell assays. Hum Reprod. 2017;32(11):2254–68.

    PubMed  CAS  Google Scholar 

  36. Du H, Naqvi H, Taylor HS. Ischemia/reperfusion injury promotes and granulocyte-colony stimulating factor inhibits migration of bone marrow-derived stem cells to endometrium. Stem Cells Dev. 2012;21(18):3324–31.

    PubMed  PubMed Central  CAS  Google Scholar 

  37. Xiao L, Song Y, Huang W, Yang S, Fu J, Feng X, et al. Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions. Reprod Biol Endocrinol. 2017;15(1):14.

    PubMed  PubMed Central  Google Scholar 

  38. Sahin Ersoy G, Zolbin MM, Cosar E, Moridi I, Mamillapalli R, Taylor HS. CXCL12 promotes stem cell recruitment and uterine repair after injury in Asherman's syndrome. Mol Ther Methods Clin Dev. 2017;4:169–77.

    PubMed  PubMed Central  CAS  Google Scholar 

  39. Azizi R, Aghebati-Maleki L, Nouri M, Marofi F, Negargar S, Yousefi M. Stem cell therapy in Asherman syndrome and thin endometrium: stem cell-based therapy. Biomed Pharmacother. 2018;102:333–43.

    PubMed  CAS  Google Scholar 

  40. Zhang Y, Lin X, Dai Y, Hu X, Zhu H, Jiang Y, et al. Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways. Reproduction. 2016;152(5):389–402.

    PubMed  CAS  Google Scholar 

  41. Wright LM, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone. 2005;36(5):840–53.

    PubMed  CAS  Google Scholar 

  42. Cao Y, Sun H, Zhu H, Zhu X, Tang X, Yan G, et al. Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial. Stem Cell Res Ther. 2018;9(1):192. https://doi.org/10.1186/s13287-018-0904-3.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gil-Sanchis C, Cervello I, Khurana S, Faus A, Verfaillie C, Simon C. Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model. Fertil Steril. 2015;103(6):1596–605.e1.

    PubMed  CAS  Google Scholar 

  44. Kilic S, Yuksel B, Pinarli F, Albayrak A, Boztok B, Delibasi T. Effect of stem cell application on Asherman syndrome, an experimental rat model. J Assist Reprod Genet. 2014;31(8):975–82.

    PubMed  PubMed Central  Google Scholar 

  45. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.

    CAS  PubMed  Google Scholar 

  46. Yang, Yan-Meng, Wan-Xi Yang. Epithelial-to-mesenchymal transition in the development of endometriosis. Oncotarget 2017;8(25):41679–89.

  47. Fan D, Wu S, Ye S, Wang W, Guo X, Liu Z. Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial. Medicine (Baltimore). 2017;96(44):e8480.

    Google Scholar 

  48. Franco HL, Dai D, Lee KY, Rubel CA, Roop D, Boerboom D, et al. WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse. FASEB J. 2011;25(4):1176–87.

    PubMed  PubMed Central  CAS  Google Scholar 

  49. Kobayashi A, Stewart CA, Wang Y, Fujioka K, Thomas NC, Jamin SP, et al. β-Catenin is essential for Müllerian duct regression during male sexual differentiation. Development. 2011;138(10):1967–75.

    PubMed  PubMed Central  CAS  Google Scholar 

  50. Yin Q, Jin P, Liu X, Wei H, Lin X, Chi C, et al. SDF-1alpha inhibits hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells through PI3K/Akt and ERK1/2 signaling pathways. Mol Biol Rep. 2011;38(1):9–16.

    PubMed  CAS  Google Scholar 

  51. Oh JE, Kim RH, Shin KH, Park NH, Kang MK. DeltaNp63α protein triggers epithelial-mesenchymal transition and confers stem cell properties in normal human keratinocytes. J Biol Chem. 2011;286(44):38757–67.

    PubMed  PubMed Central  CAS  Google Scholar 

  52. Zhao J, Chen Q, Cai D, Duan Z, Li X, Xue X. Dominant factors affecting reproductive outcomes of fertility-desiring young women with intrauterine adhesions. Arch Gynecol Obstet. 2017;295(4):923–7.

    PubMed  Google Scholar 

  53. Huang H, Cheng C, Johnson G, Wang R, Xue M, Zhang A, et al. Hysteroscopic intrauterine adhesiolysis using a blunt spreading dissection technique with double-action forceps. J Minim Invasive Gynecol. 2018;25(4):583–4.

    PubMed  Google Scholar 

  54. Patterson AL, Zhang L, Arango NA, Teixeira J, Pru JK. Mesenchymal-to-epithelial transition contributes to endometrial regeneration following natural and artificial decidualization. Stem Cells Dev. 2013;22(6):964–74.

    PubMed  CAS  Google Scholar 

  55. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.

    PubMed  CAS  Google Scholar 

  56. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815–22.

    PubMed  CAS  Google Scholar 

  57. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro- inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS One. 2010;5(4):e10088.

    PubMed  PubMed Central  Google Scholar 

  58. Gan L, Duan H, Xu Q, Tang YQ, Li JJ, Sun FQ, et al. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions. Cytotherapy. 2017;19(5):603–16.

    PubMed  CAS  Google Scholar 

  59. Liu D, Wang J, Zhao G, Jiang P, Song M, Ding H, et al. CSF1-associated decrease in endometrial macrophages may contribute to Asherman's syndrome. Am J Reprod Immunol. 2020;83(1):e13191.

    PubMed  Google Scholar 

  60. Bozorgmehr M, Moazzeni SM, Salehnia M, Sheikhian A, Nikoo S, Zarnani AH. Menstrual blood-derived stromal stem cells inhibit optimal generation and maturation of human monocyte-derived dendritic cells. Immunol Lett. 2014;162(2 Pt B):239–46.

    PubMed  CAS  Google Scholar 

  61. Schneider C, von Aulock S, Zedler S, Schinkel C, Hartung T, Faist E. Perioperative recombinant human granulocyte colony-stimulating factor (Filgrastim) treatment prevents immunoinflammatory dysfunction associated with major surgery. Ann Surg. 2004;239(1):75–81.

    PubMed  PubMed Central  Google Scholar 

  62. Sabry D, Mostafa A, Marzouk S, Ibrahim W, Ali HHM, Hassan A, et al. Neupogen and mesenchymal stem cells are the novel therapeutic agents in regeneration of induced endometrial fibrosis in experimental rats. Biosci Rep. 2017;37(5):BSR20170794.

    PubMed  PubMed Central  CAS  Google Scholar 

  63. Meisel R, Brockers S, Heseler K, Degistirici O, Bulle H, Woite C, et al. Human but not murine multipotent mesenchymal stromal cells exhibit broad- spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase. Leukemia. 2011;25(4):648–54.

    PubMed  CAS  Google Scholar 

  64. Cortes-Araya Y, Amilon K, Rink BE, Black G, Lisowski Z, Donadeu FX, et al. Comparison of antibacterial and immunological properties of Mesenchymal stem/stromal cells from equine bone marrow, endometrium, and adipose tissue. Stem Cells Dev. 2018;27(21):1518–25.

    PubMed  PubMed Central  CAS  Google Scholar 

  65. Balan A, Lucchini G, Schmidt S, Schneider A, Tramsen L, Kuci S, et al. Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease—friends or foes? Leukemia. 2014;28(10):1941–8.

    PubMed  CAS  Google Scholar 

  66. Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells. 2010;28(12):2229–38.

    PubMed  PubMed Central  CAS  Google Scholar 

  67. Domnina A, Novikova P, Obidina J, Fridlyanskaya I, Alekseenko L, Kozhukharova I, et al. Human mesenchymal stem cells in spheroids improve fertility in model animals with damaged endometrium. Stem Cell Res Ther. 2018;9(1):50. https://doi.org/10.1186/s13287-018-0801-9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Queckborner S, Syk Lundberg E, Gemzell-Danielsson K, Davies LC. Endometrial stromal cells exhibit a distinct phenotypic and immunomodulatory profile. Stem Cell Res Ther. 2020;11(1):15. https://doi.org/10.1186/s13287-019-1496-2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Lai D, Wang F, Yao X, Zhang Q, Wu X, Xiang C. Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure. J Transl Med. 2015;13:155. https://doi.org/10.1186/s12967-015-0516-y.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Patel AN, Park E, Kuzman M, Benetti F, Silva FJ, Allickson JG. Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation. Cell Transplant. 2008;17(3):303–11.

    PubMed  Google Scholar 

  71. Chen L, Qu J, Xiang C. The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine. Stem Cell Res Ther. 2019;10(1):1. https://doi.org/10.1186/s13287-018-1105-9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Li Y, Li X, Zhao H, Feng R, Zhang X, Tai D, et al. Efficient induction of pluripotent stem cells from menstrual blood. Stem Cells Dev. 2013;22(7):1147–58.

    PubMed  CAS  Google Scholar 

  73. Zheng SX, Wang J, Wang XL, Ali A, Wu LM, Liu YS. Feasibility analysis of treating severe intrauterine adhesions by transplanting menstrual blood-derived stem cells. Int J Mol Med. 2018;41(4):2201–12.

    PubMed  CAS  Google Scholar 

  74. Zhu H, Pan Y, Jiang Y, Li J, Zhang Y, Zhang S. Activation of the Hippo/TAZ pathway is required for menstrual stem cells to suppress myofibroblast and inhibit transforming growth factor beta signaling in human endometrial stromal cells. Hum Reprod. 2019;34(4):635–45.

    PubMed  CAS  Google Scholar 

  75. Hamid AA, Joharry MK, Mun-Fun H, Hamzah SN, Rejali Z, Yazid MN, et al. Highly potent stem cells from full-term amniotic fluid: a realistic perspective. Reprod Biol. 2017;17(1):9–18.

    PubMed  Google Scholar 

  76. Loukogeorgakis SP, De Coppi P. Concise review: amniotic fluid stem cells: the known, the unknown, and potential regenerative medicine applications. Stem Cells. 2017;35(7):1663–73.

    PubMed  Google Scholar 

  77. Dziadosz M, Basch RS, Young BK. Human amniotic fluid: a source of stem cells for possible therapeutic use. Am J Obstet Gynecol. 2016;214(3):321–7.

    PubMed  Google Scholar 

  78. Rombouts WJ, Ploemacher RE. Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia. 2003;17(1):160–70.

    PubMed  CAS  Google Scholar 

  79. Liu Y, Tal R, Pluchino N, Mamillapalli R, Taylor HS. Systemic administration of bone marrow-derived cells leads to better uterine engraftment than use of uterine-derived cells or local injection. J Cell Mol Med. 2018;22(1):67–76.

    PubMed  Google Scholar 

  80. Zhao J, Zhang Q, Wang Y, Li Y. Uterine infusion with bone marrow mesenchymal stem cells improves endometrium thickness in a rat model of thin endometrium. Reprod Sci. 2015;22(2):181–8. https://doi.org/10.1177/1933719114537715 Erratum in: Reprod Sci. 2019 Dec;26(12):1666–1667. Erratum in: Reprod Sci. 2019 Oct;26(10):1401–1402. PMID: 24947483; PMCID: PMC4287599.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Watson N, Divers R, Kedar R, Mehindru A, Mehindru A, Borlongan MC, et al. Discarded Wharton jelly of the human umbilical cord: a viable source for mesenchymal stromal cells. Cytotherapy. 2015;17(1):18–24.

    PubMed  Google Scholar 

  82. Shi Q, Gao J, Jiang Y, Sun B, Lu W, Su M, et al. Differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells into endometrial cells. Stem Cell Res Ther. 2017;8(1):246. https://doi.org/10.1186/s13287-017-0700-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Zhao YX, Chen SR, Su PP, Huang FH, Shi YC, Shi QY, et al. Using Mesenchymal stem cells to treat female infertility: an update on female reproductive diseases. Stem Cells Int. 2019;2019:9071720.

    PubMed  PubMed Central  Google Scholar 

  84. Yang ZX, Han ZB, Ji YR, Wang YW, Liang L, Chi Y, et al. CD106 identifies a subpopulation of mesenchymal stem cells with unique immunomodulatory properties. PLoS One. 2013;8(3):e59354.

    PubMed  PubMed Central  CAS  Google Scholar 

  85. Zhang L, Li Y, Guan CY, Tian S, Lv XD, Li JH, et al. Therapeutic effect of human umbilical cord-derived mesenchymal stem cells on injured rat endometrium during its chronic phase. Stem Cell Res Ther. 2018;9(1):36. https://doi.org/10.1186/s13287-018-0777-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Ebrahim N, Mostafa O, El Dosoky RE, Ahmed IA, Saad AS, Mostafa A, et al. Human mesenchymal stem cell-derived extracellular vesicles/estrogen combined therapy safely ameliorates experimentally induced intrauterine adhesions in a female rat model. Stem Cell Res Ther. 2018;9(1):175.

    PubMed  PubMed Central  CAS  Google Scholar 

  87. Parolini O, Alviano F, Bagnara GP, Bilic G, Bühring HJ, Evangelista M, et al. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international workshop on placenta derived stem cells. Stem Cells. 2008;26(2):300–11.

    PubMed  Google Scholar 

  88. James JL, Srinivasan S, Alexander M, Chamley LW. Can we fix it? Evaluating the potential of placental stem cells for the treatment of pregnancy disorders. Placenta. 2014;35(2):77–84.

    PubMed  CAS  Google Scholar 

  89. Chang CW, Parast MM. Human trophoblast stem cells: real or not real? Placenta. 2017;60(Suppl 1):S57–60.

    PubMed  PubMed Central  CAS  Google Scholar 

  90. König J, Weiss G, Rossi D, Wankhammer K, Reinisch A, Kinzer M, et al. Placental mesenchymal stromal cells derived from blood vessels or avascular tissues: what is the better choice to support endothelial cell function? Stem Cells Dev. 2015;24(1):115–31.

    PubMed  Google Scholar 

  91. Komaki M, Numata Y, Morioka C, Honda I, Tooi M, Yokoyama N, et al. Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis. Stem Cell Res Ther. 2017;8(1):219.

    PubMed  PubMed Central  Google Scholar 

  92. Luan X, Li G, Wang G, Wang F, Lin Y. Human placenta-derived mesenchymal stem cells suppress T cell proliferation and support the culture expansion of cord blood CD34+ cells: a comparison with human bone marrow-derived mesenchymal stem cells. Tissue Cell. 2013;45(1):32–8.

    PubMed  CAS  Google Scholar 

  93. Wu M, Zhang R, Zou Q, Chen Y, Zhou M, Li X, et al. Comparison of the biological characteristics of Mesenchymal stem cells derived from the human placenta and umbilical cord. Sci Rep. 2018;8(1):5014.

    PubMed  PubMed Central  Google Scholar 

  94. Du W, Li X, Chi Y, Ma F, Li Z, Yang S, et al. VCAM-1+ placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity. Stem Cell Res Ther. 2016;7:49.

    PubMed  PubMed Central  Google Scholar 

  95. Li B, Zhang Q, Sun J, Lai D. Human amniotic epithelial cells improve fertility in an intrauterine adhesion mouse model. Stem Cell Res Ther. 2019;10(1):257.

    PubMed  PubMed Central  Google Scholar 

  96. McIntyre JA, Jones IA, Danilkovich A, Vangsness CT Jr. The placenta: applications in orthopaedic sports medicine. Am J Sports Med. 2018;46(1):234–47.

    PubMed  Google Scholar 

  97. Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17(1):11–22.

    PubMed  CAS  Google Scholar 

  98. Balbi C, Bollini S. Fetal and perinatal stem cells in cardiac regeneration: moving forward to the paracrine era. Placenta. 2017;59:96–106.

    PubMed  CAS  Google Scholar 

  99. Pischiutta F, Sammali E, Parolini O, Carswell HVO, Zanier ER. Placenta-derived cells for acute brain injury. Cell Transplant. 2018;27(1):151–67.

    PubMed  PubMed Central  Google Scholar 

  100. Vanover M, Wang A, Farmer D. Potential clinical applications of placental stem cells for use in fetal therapy of birth defects. Placenta. 2017;59:107–12.

    PubMed  Google Scholar 

  101. Heo JS, Choi Y, Kim HS, Kim HO. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue. Int J Mol Med. 2016;37(1):115–25.

    PubMed  Google Scholar 

  102. Lee SY, Shin JE, Kwon H, Choi DH, Kim JH. Effect of autologous adipose-derived stromal vascular fraction transplantation on endometrial regeneration in patients of Asherman's syndrome: a pilot study. Reprod Sci. 2020;27(2):561–8.

    PubMed  Google Scholar 

  103. Jun SM, Park M, Lee JY, Jung S, Lee JE, Shim SH, et al. Single cell-derived clonally expanded mesenchymal progenitor cells from somatic cell nuclear transfer-derived pluripotent stem cells ameliorate the endometrial function in the uterus of a murine model with Asherman's syndrome. Cell Prolif. 2019;52(3):e12597.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics & Gynecology, Maimonides Medical Center, 967 48th St., Brooklyn, NY, 11219, USA

    Ariel Benor

  2. Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA

    Steven Gay & Alan DeCherney

  3. Department of Reproductive Endocrinology & Infertility, NICHD, NIH, Bethesda, MD, USA

    Steven Gay & Alan DeCherney

Authors
  1. Ariel Benor
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  2. Steven Gay
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  3. Alan DeCherney
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Correspondence to Ariel Benor.

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Benor, A., Gay, S. & DeCherney, A. An update on stem cell therapy for Asherman syndrome. J Assist Reprod Genet 37, 1511–1529 (2020). https://doi.org/10.1007/s10815-020-01801-x

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  • DOI: https://doi.org/10.1007/s10815-020-01801-x

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