Vol 93, No 11 (2022)
Research paper
Published online: 2022-10-03

open access

Page views 3886
Article views/downloads 426
Get Citation

Connect on Social Media

Connect on Social Media

Endometrial regeneration in Asherman’s syndrome and endometrial atrophy using Wharton’s jelly-derived mesenchymal stem cells

Jaroslaw B. Kaczynski12, Jakub K. Rzepka12
Pubmed: 36196566
Ginekol Pol 2022;93(11):904-909.


Objectives: Reconstruction of the endometrium in patients with endometrial atrophy and Asherman’s syndrome using
Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs).

Material and methods: Prospective pilot study, with the inclusion of two patients.

Results: After administration of WJ-MSCs into the uterine cavity, endometrial reconstruction was achieved in both patients. Pregnancy was achieved in one of them, after transfer of a frozen embryo, completed by delivery around the due date.

Conclusions: Endometrial atrophy and Asherman’s syndrome, is one of the most frustrating clinical situations we face
in assisted reproductive procedures. The use of Wharton’s jelly-derived mesenchymal stem cells in restoring the normal
function of the endometrium, could become an easy and accessible therapeutic medal, for this endometrial dysfunction,
which is so difficult to treat.

Article available in PDF format

View PDF Download PDF file


  1. Broekmans FJ, Broer SL, Fauser B, Macklon N. Prognostic testing for ovarian reserve. In: Gardner DK, Weissman A, Howles C, Shoaham Z. ed. Taxtbook of Assisted Reproductive Techniques. Vol. 2: Clinical Perspectives. Four Edition. Informa Healthcare 2012: [numery stron ??].
  2. Chan J, Vilella F, Dey SKM. Molecular interplay in successful implantation. In: Sanders S. ed. Ten Critical Topics in Reproductive Medicine. Science/AAAS, Washington, DC 2013.
  3. Paiva P, Hannan NJ, Hincks C, et al. Human chorionic gonadotrophin regulates FGF2 and other cytokines produced by human endometrial epithelial cells, providing a mechanism for enhancing endometrial receptivity. Hum Reprod. 2011; 26(5): 1153–1162.
  4. Senturk LM, Erel CT. Thin endometrium in assisted reproductive technology. Curr Opin Obstet Gynecol. 2008; 20(3): 221–228.
  5. Paulson RJ. Hormonal induction of endometrial receptivity. Fertil Steril. 2011; 96(3): 530–535.
  6. Vitagliano A, Di Spiezio Sardo A, Saccone G, et al. Endometrial scratch injury for women with one or more previous failed embryo transfers: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2018; 110(4): 687–702.e2.
  7. Yu D, Wong YM, Cheong Y, et al. Asherman syndrome – one century later. Fertil Steril. 2008; 89(4): 759–779.
  8. Panayotidis C, Weyers S, Bosteels J, et al. Intrauterine adhesions (IUA): has there been progress in understanding and treatment over the last 20 years? Gynecological Surgery. 2008; 6(3): 197–211.
  9. Lo ST, Ramsay P, Pierson R, et al. Endometrial thickness measured by ultrasound scan in women with uterine outlet obstruction due to intrauterine or upper cervical adhesions. Hum Reprod. 2008; 23(2): 306–309.
  10. Valle RF, Sciarra JJ. Intrauterine adhesions: hysteroscopic diagnosis, classification, treatment, and reproductive outcome. Am J Obstet Gynecol. 1988; 158(6 Pt 1): 1459–1470.
  11. Coccia ME, Becattini C, Bracco GL, et al. Pressure lavage under ultrasound guidance: a new approach for outpatient treatment of intrauterine adhesions. Fertil Steril. 2001; 75(3): 601–606.
  12. Fernandez H, Al-Najjar F, Chauveaud-Lambling A, et al. Fertility after treatment of Asherman's syndrome stage 3 and 4. J Minim Invasive Gynecol. 2006; 13(5): 398–402.
  13. Dowd MJ, Phillipp EE. The History of Obstetrics and Gynaecology . Parthenon Publishing, New York 1994: 55–82.
  14. Croxatto HB, Ortiz ME, Díaz S, et al. Studies on the duration of egg transport by the human oviduct. II. Ovum location at various intervals following luteinizing hormone peak. Am J Obstet Gynecol. 1978; 132(6): 629–634.
  15. Croxatto HB. Physiology of gamete and embryo transport through the fallopian tube. Reprod Biomed Online. 2002; 4(2): 160–169.
  16. Pojda Z, Machaj E, Kurzyk A. Mezenchymalne komórki macierzyste. Postępy Biochem. 2013; 59(2): 187–197.
  17. Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med. 2004; 8(3): 301–316.
  18. Horwitz EM, Le Blanc K, Dominici M, et al. International Society for Cellular Therapy. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 2005; 7(5): 393–395.
  19. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4): 315–317.
  20. Troyer DL, Weiss ML. Wharton's jelly-derived cells are a primitive stromal cell population. Stem Cells. 2008; 26(3): 591–599.
  21. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001; 7(2): 211–228.
  22. Björntorp P, Karlsson M, Pertoft H, et al. Isolation and characterization of cells from rat adipose tissue developing into adipocytes. J Lipid Res. 1978; 19(3): 316–324.
  23. Hauner H, Entenmann G, Wabitsch M, et al. Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest. 1989; 84(5): 1663–1670.
  24. Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M, et al. Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. Cytotherapy. 2006; 8(2): 166–177.
  25. Borlongan CV, Hadman M, Sanberg CD, et al. Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke. Stroke. 2004; 35(10): 2385–2389.
  26. Grinnemo KH, Månsson A, Dellgren G, et al. Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium. J Thorac Cardiovasc Surg. 2004; 127(5): 1293–1300.
  27. Seo MJ, Suh SuY, Bae YC, et al. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun. 2005; 328(1): 258–264.
  28. Taléns-Visconti R, Bonora A, Jover R, et al. Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol. 2006; 12(36): 5834–5845.
  29. Karaoz E, Okcu A, Ünal ZS, et al. Adipose tissue-derived mesenchymal stromal cells efficiently differentiate into insulin-producing cells in pancreatic islet microenvironment both in vitro and in vivo. Cytotherapy. 2013; 15(5): 557–570.
  30. Marappagounder D, Somasundaram I, Dorairaj S, et al. Differentiation of mesenchymal stem cells derived from human bone marrow and subcutaneous adipose tissue into pancreatic islet-like clusters in vitro. Cell Mol Biol Lett. 2013; 18(1): 75–88.
  31. Timper K, Seboek D, Eberhardt M, et al. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun. 2006; 341(4): 1135–1140.
  32. Fu YS, Cheng YC, Lin MYA, et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells. 2006; 24(1): 115–124.
  33. Jomura S, Uy M, Mitchell K, et al. Potential treatment of cerebral global ischemia with Oct-4+ umbilical cord matrix cells. Stem Cells. 2007; 25(1): 98–106.
  34. Lund RD, Wang S, Lu B, et al. Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease. Stem Cells. 2007; 25(3): 602–611.
  35. Lu LL, Liu YJ, Yang SG, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica. 2006; 91(8): 1017–1026.
  36. Sarugaser R, Lickorish D, Baksh D, et al. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 2005; 23(2): 220–229.
  37. Weiss ML, Medicetty S, Bledsoe AR, et al. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells. 2006; 24(3): 781–792.
  38. Cho PS, Messina DJ, Hirsh EL, et al. Immunogenicity of umbilical cord tissue derived cells. Blood. 2008; 111(1): 430–438.
  39. Cervelló I, Gil-Sanchis C, Mas A, et al. Bone marrow-derived cells from male donors do not contribute to the endometrial side population of the recipient. PLoS One. 2012; 7(1): e30260.
  40. Wang XY, Lan Yu, He WY, et al. Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos. Blood. 2008; 111(4): 2436–2443.
  41. Taghizadeh RR, Cetrulo KJ, Cetrulo CL. Wharton's Jelly stem cells: future clinical applications. Placenta. 2011; 32 Suppl 4: S311–S315.
  42. Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004; 292(1): 81–85.
  43. 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): 43–48.
  44. Santamaria X, Cabanillas S, Cervelló 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): 1087–1096.
  45. Gargett CE, Healy DL. Generating receptive endometrium in Asherman's syndrome. J Hum Reprod Sci. 2011; 4(1): 49–52.
  46. Gargett CE, Ye L. Endometrial reconstruction from stem cells. Fertil Steril. 2012; 98(1): 11–20.