Endometrial Regeneration in Asherman's Syndrome: Clinical and Translational evidence of Stem Cell Therapies

Author(s): Xuejing Hou, Ying Liu*, Isabelle Streuli, Patrick Dällenbach, Jean Dubuisson, Yveline Ansaldi, Nicola Pluchino*.

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 6 , 2019

Become EABM
Become Reviewer


Asherman’s Syndrome or Intrauterine adhesions is an acquired uterine condition where fibrous scarring forms within the uterine cavity, resulting in reduced menstrual flow, pelvic pain and infertility. Until recently, the molecular mechanisms leading to the formation of fibrosis were poorly understood, and the treatment of Asherman’s syndrome has largely focused on hysteroscopic resection of adhesions, hormonal therapy, and physical barriers. Numerous studies have begun exploring the molecular mechanisms behind the fibrotic process underlying Asherman’s Syndrome as well as the role of stem cells in the regeneration of the endometrium as a treatment modality. The present review offers a summary of available stem cell-based regeneration studies, as well as highlighting current gaps in research.

Keywords: Endometrium, Asherman's syndrome, intrauterine adhesions, stem cells, scaffold, human embryonic stem cells.

Smikle C, Bhimji SS. Asherman Syndrome. In StatPearls, StatPearls Publishing StatPearls Publishing LLC Treasure Island (FL) 2018.
Craig VJ, Zhang L, Hagood JS, et al. Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 2015; 53(5): 585-600.
Yu D, Wong YM, Cheong Y. Asherman syndrome--one century later. Fertil Steril 2008; 89(4): 759-79.
Gargett CE, Ye L. Endometrial reconstruction from stem cells. Fertil Steril 2012; 98(1): 11-20.
Azizi R, Aghebati-Maleki L, Nouri M, et al. Stem cell therapy in Asherman syndrome and thin endometrium: Stem cell- based therapy. Biomed Pharmacother 2018; 102: 333-43.
Louie Y, Robyn M, Lo CY, et al. Generation of human female reproductive tract epithelium from human embryonic stem cells. PLoS One 2011; 6(6)e21136
Jing Z, Qiong Z, Yonggang W, et al. Rat bone marrow mesenchymal stem cells improve regeneration of thin endometrium in rat. Fertil Steril 2014; 101(2): 587-94.
Jia S, Liu X, Li W, Xie J, Yang L, Li L. Peroxisome proliferator-activated receptor gamma negatively regulates the differentiation of bone marrow-derived mesenchymal stem cells toward myofibroblasts in liver fibrogenesis. Cell Physiol Biochem 2015; 37(6): 2085-100.
Mezey E, Key S, Vogelsang G, et al. Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci USA 2003; 100(3): 1364-9.
Wu J, Niu J, Li X, et al. Hypoxia induces autophagy of bone marrow-derived mesenchymal stem cells via activation of ERK1/2. Cell Physiol Biochem 2014; 33(5): 1467-74.
Korbling M, Katz RL, Khanna A, et al. Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Engl J Med 2002; 346(10): 738-46.
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.
Feryal A, Hongling D, Hakan C, et al. Bone Marrow-Derived Stem Cell (BMDSC) transplantation improves fertility in a murine model of Asherman’s syndrome. PLoS One 2014; 9(5)e96662
Sahin Ersoy G, Zolbin MM, Cosar E, et al. CXCL12 promotes stem cell recruitment and uterine repair after injury in asherman’s syndrome. Mol Ther Methods Clin Dev 2017; 4: 169-77.
Ding L, Li X, Sun H, et al. Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus. Biomaterials 2014; 35(18): 4888-900.
Liu Y, Tal R, Pluchino N, et al. 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.
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.
Santamaria X, Cabanillas S, Cervello I, 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.
Ye L, Mayberry R, Lo CY, et al. Generation of human female reproductive tract epithelium from human embryonic stem cells. PLoS One 2011; 6(6)e21136
Song T, Zhao X, Sun H, et al. Regeneration of uterine horns in rats using collagen scaffolds loaded with human embryonic stem cell-derived endometrium-like cells. Tissue Eng Part A 2015; 21(1-2): 353-61.
Suzuki DE, Nakahata AM, Okamoto OK. Knockdown of E2F2 inhibits tumorigenicity, but preserves stemness of human embryonic stem cells. Stem Cells Dev 2014; 23(11): 1266-74.
Y.Q. Tang, L. Gan, Q. Xu, S. Wang, J.J. Li, H. Duan. Effects of human umbilical cord mesenchymal stem cells on intrauterine adhesions in a rat model. Int J Clin Exp Pathol 2016; 9(11): 12119-29.
Zhang L, Li Y, Guan CY, 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.
Xu L, Ding L, Wang L, et al. Umbilical cord-derived mesenchymal stem cells on scaffolds facilitate collagen degradation via upregulation of MMP-9 in rat uterine scars. Stem Cell Res Ther 2017; 8(1): 84.
Cao Y, Sun H, Zhu H, 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.
Gan L, Duan H, Xu Q, et al. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions. Cytotherapy 2017; 19(5): 603-16.
Singh N, Mohanty S, Seth T, et al. Autologous stem cell transplantation in refractory Asherman’s syndrome: A novel cell based therapy. J Hum Reprod Sci 2014; 7(2): 93-8.
Allickson JG, Sanchez A, Yefimenko N, Borlongan CV, Sanberg PR. Recent studies assessing the proliferative capability of a novel adult stem cell identified in menstrual blood. Open Stem Cell J 2011; 3(2011): 4-10.
Tan J, Li P, Wang Q, et al. Autologous menstrual blood-derived stromal cells transplantation for severe Asherman’s syndrome. Hum Reprod 2016; 31(12): 2723-9.
Zhu H, Jiang Y, Pan Y, Shi L, Zhang S. Human menstrual blood-derived stem cells promote the repair of impaired endometrial stromal cells by activating the p38 MAPK and AKT signaling pathways. Reprod Biol 2018; 18(3): 274-81.
Masuda H, Matsuzaki Y, Hiratsu E, et al. Stem cell-like properties of the endometrial side population: Implication in endometrial regeneration. PLoS One 2010; 5e10387
Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 2004; 292(1): 81-5.
Gargett CE, Schwab KE, Deane JA. Endometrial stem/progenitor cells: The first 10 years. Hum Reprod Update 2016; 22(2): 137-63.
Schwab KE, Gargett CE. Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod 2007; 22(11): 2903-11.
Masuda H, Anwar SS, Buhring HJ, Rao JR, Gargett CE. A novel marker of human endometrial mesenchymal stem-like cells. Cell Transplant 2012; 21(10): 2201-14.
Shamosi A, Mehrabani D, Azami M, et al. Differentiation of human endometrial stem cells into endothelial-like cells on gelatin/chitosan/bioglass nanofibrous scaffolds. Artif Cells Nanomed Biotechnol 2017; 45(1): 163-73.
Shoae-Hassani A, Sharif S, Seifalian AM, et al. Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women. BJU Int 2013; 112(6): 854-63.
Simoni M, Taylor HS. Therapeutic strategies involving uterine stem cells in reproductive medicine. Curr Opin Obstet Gynecol 2018; 30(3): 209-16.
Darzi S, Werkmeister JA, Deane JA, Gargett CE. Identification and characterization of human endometrial mesenchymal stem/stromal cells and their potential for cellular therapy. Stem Cells Transl Med 2016; 5(9): 1127-32.
Domnina A, Novikova P, Obidina J, et al. Human mesenchymal stem cells in spheroids improve fertility in model animals with damaged endometrium. Stem Cell Res Ther 2018; 9(1): 50.
Rink BE, Beyer T, French HM, Watson E, Aurich C, Donadeu FX. The fate of autologous endometrial mesenchymal stromal cells after application in the healthy equine uterus. Stem Cells Dev 2018; 27(15): 1046-52.
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.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [454 - 459]
Pages: 6
DOI: 10.2174/1574888X14666190213100528
Price: $58

Article Metrics

PDF: 60