Comparison of the regenerative effects of bone marrow/adipose-derived stem cells in the Asherman model following local or systemic administration
other
OA: green
public-domain-us
⤵ 1 in-corpus citation
AI-generated summary
Local injection of adipose-derived stem cells in a rat Asherman's syndrome model reduced fibrosis and increased endometrial thickness more effectively than bone marrow-derived stem cells.
One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works
AI-generated deep summary
This paper studied how bone marrow-derived mesenchymal stem cells (BMSCs) versus adipose-derived mesenchymal stem cells (AMSCs), delivered either by local intrauterine injection or by intravenous (systemic) injection, affect endometrial regeneration in adult Wistar rats with Asherman’s syndrome. After Asherman’s syndrome was induced, CM-Dil–positive stem cells were administered, and 3 weeks later the authors assessed endometrial thickness, collagen deposition (fibrosis), stem cell migration/retention in damaged endometrium, and VEGF expression using histochemistry and immunofluorescence. All stem cell-treated groups showed amelioration of damaged endometrium, with reduced collagen in both systemic and local injection groups, and local injection of MSCs showing decreased fibrosis relative to other groups; locally injected BMSCs and AMSCs increased endometrial thickness more than systemic AMSCs, while systemic BMSCs produced the highest VEGF expression but the fewest retained CM-Dil+ cells. The paper’s limitation is its reliance on a rat model with short-term (3-week) histologic and molecular readouts rather than long-term functional or fertility outcomes, and it does not fully resolve the mechanism behind differences between cell sources and routes. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works
Abstract
PURPOSE: Cell therapy is a promising strategy for the treatment of Asherman's syndrome (AS), but the origin of these cells and injection route influence the therapeutic effect and complications of cell therapy. Herein, we compared the effects of systemic or local intrauterine injection of bone marrow or adipose-derived mesenchymal stem cells (BMSCs/AMSCs) on the endometrium in a rat model of AS.
METHODS: After induction of AS in adult Wistar rats, the CM-Dil-positive BMSCs or AMSCs were injected either locally or intravenously. After 3 weeks, endometrial thickness, collagen deposition, cell migration, and VEGF expression were evaluated using histochemistry/immunofluorescence studies.
RESULTS: In all stem cell-treated groups, an ameliorative effect on the damaged endometrium was noted. Collagen deposition diminished in both groups (IV and local injection) compared to the AS model. In rats injected locally with MSC, fibrosis decreased compared to the other groups. Moreover, endometrial thickness increased in the groups that received local injection of BMSCs and AMSCs more than the IV-transplanted AMSCs group. Immunofluorescent staining demonstrated that although the systemic transplantation of BMSCs was more effective than the other groups on VEGF expression, it led to the lowest number of CM-Dil+ stem cells in the damaged endometrium.
CONCLUSION: Stem cell transplantation may reconstruct the damaged endometrium, but it is recommended to select the most effective stem cells and injection route. Because the removal of the fibrosis and the replacement of the epithelia cells is an effective therapeutic strategy for AS, in this study, we conclude that the local injection of AMSCs is more appropriate than BMSCs to treat AS.
Full text
8,621 characters
· extracted from
oa-doi-fallback
· 5 sections
· click to expand
Abstract
Purpose
Cell therapy is a promising strategy for the treatment of Asherman’s syndrome (AS), but the origin of these cells and injection route influence the therapeutic effect and complications of cell therapy. Herein, we compared the effects of systemic or local intrauterine injection of bone marrow or adipose-derived mesenchymal stem cells (BMSCs/AMSCs) on the endometrium in a rat model of AS.
Methods
After induction of AS in adult Wistar rats, the CM-Dil-positive BMSCs or AMSCs were injected either locally or intravenously. After 3 weeks, endometrial thickness, collagen deposition, cell migration, and VEGF expression were evaluated using histochemistry/immunofluorescence studies.
Results
In all stem cell-treated groups, an ameliorative effect on the damaged endometrium was noted. Collagen deposition diminished in both groups (IV and local injection) compared to the AS model. In rats injected locally with MSC, fibrosis decreased compared to the other groups. Moreover, endometrial thickness increased in the groups that received local injection of BMSCs and AMSCs more than the IV-transplanted AMSCs group. Immunofluorescent staining demonstrated that although the systemic transplantation of BMSCs was more effective than the other groups on VEGF expression, it led to the lowest number of CM-Dil+ stem cells in the damaged endometrium.
Conclusion
Stem cell transplantation may reconstruct the damaged endometrium, but it is recommended to select the most effective stem cells and injection route. Because the removal of the fibrosis and the replacement of the epithelia cells is an effective therapeutic strategy for AS, in this study, we conclude that the local injection of AMSCs is more appropriate than BMSCs to treat AS.
Similar content being viewed by others
References
Asherman JG. Amenorrhoea traumatica (atretica). BJOG Int J Obstet Gynaecol. 1948;55(1):23–30.
Westendorp IC, Ankum WM, Mol BW, Vonk J. Prevalence of Asherman’s syndrome after secondary removal of placental remnants or a repeat curettage for incomplete abortion. Human Reprod. 1998;13(12):3347–50.
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(1):118.
Yu D, Li T-C, Xia E, Huang X, Liu Y, Peng X. Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman’s syndrome. Fertil Steril. 2008;89(3):715–22.
Gargett CE, Schwab KE, Deane JA. Endometrial stem/progenitor cells: the first 10 years. Hum Reprod Update. 2016;22(2):137–63.
Queckborner S, Davies LC, von Grothusen C, Santamaria X, Simon C, Gemzell-Danielsson K. Cellular therapies for the endometrium: an update. Acta Obstet Gynecol Scand. 2019;98(5):672–7.
Ersoy GS, 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.
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.
Saribas GS, Ozogul C, Tiryaki M, Pinarli FA, Kilic SH. Effects of uterus derived mesenchymal stem cells and their exosomes on Asherman’s syndrome. Acta Histochem. 2020;122(1):151465.
Gao L, Huang Z, Lin H, Tian Y, Li P, Lin S. Bone marrow mesenchymal stem cells (BMSCs) restore functional endometrium in the rat model for severe Asherman syndrome. Reprod Sci. 2019;26(3):436–44.
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.
Zhao G, Cao Y, Zhu X, Tang X, Ding L, Sun H, Li J, Li X, Dai C, Ru T, Zhu H, Lu J, Lin C, Wang J, Yan G, Wang H, Wang L, Dai Y, Wang B, Li R, Dai J, Zhou Y, Hu Y. Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman's syndrome. Sci China Life Sci. 2017;60(4):404–16.
Noel D, Caton D, Roche S, Bony C, Lehmann S, Casteilla L, et al. Cell specific differences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation potentials. Exp Cell Res. 2008;314(7):1575–84. https://doi.org/10.1016/jyexcr200712022 Epub 2008 Jan 12.
Zhu X, Shi W, Tai W, Liu F. The comparition of biological characteristics and multilineage differentiation of bone marrow and adipose derived mesenchymal stem cells. Cell Tissue Res. 2012;350(2):277–87. https://doi.org/10.1007/s00441-012-1453-1 Epub 2012 Jun 5.
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.
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. https://doi.org/10.1371/journalpone0096662 eCollection 2014.
Shao X, Ai G, Wang L, Qin J, Li Y, Jiang H, et al. Adipose-derived stem cells transplantation improves endometrial injury repair. Zygote. 2019;27(6):367–74. https://doi.org/10.1017/S096719941900042X Epub 2019 Aug 27.
Hadi AM, Mouchaers KTB, Schalij I, Grunberg K, Meijer GA, Vonk-Noordegraaf A, et al. Rapid quantification of myocardial fibrosis: a new macro-based automated analysis. Cell Oncol. 2010;34(4):343–54.
Monsef F, Artimani T, Alizadeh Z, Mahdi R, Solgi G, Yavangi M, et al. Effects of adipose- derived stromal vascular fraction on Asherman syndrome model. Acta Histochem. 2020;122(5):151556.
Koohestani F, Braundmeier AG, Mahdian A, Seo J, Bi J, Nowak RA. Extracellular matrix collagen alters cell proliferation and cell cycle progression of human uterine leiomyoma smooth muscle cells. PLoS One. 2013;8(9):e75844. https://doi.org/10.1371/journalpone0075844 eCollection 2013.
Gargett CE, Masuda H. Adult stem cells in the endometrium. Mol Hum Reprod. 2010;16(11):818–34. https://doi.org/10.1093/molehr/gaq061 Epub 2010 Jul 13.
Hu J, Yuan R. The expression levels of stem cell markers importin13, c-kit, CD146, and telomerase are decreased in endometrial polyps. Med Sci Monit. 2011;17(8):BR221–7. https://doi.org/10.12659/msm881901.
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.
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.
Malhotra N, Bahadur A, Kalaivani M, Mittal S. Changes in endometrial receptivity in women with Asherman’s syndrome undergoing hysteroscopic adhesiolysis. Arch Gynecol Obstet. 2012;286(2):525–30. https://doi.org/10.1007/s00404-012-2336-0 Epub 2012 Apr 26.
Unger JB, Meeks GR. Hysterectomy after endometrial ablation. Am J Obstet Gynecol. 1996;175(6):1432–6; discussion 1436–7. https://doi.org/10.1016/s0002-9378(96)70086-8.
Su J, Li ZQ, Cui S, Ji LH, Chai KX, Geng H, et al. The expressions of VEGF and VEGFR signaling pathway in the bone marrow mononuclear cells with chronic mountain sickness. Zhonghua Yi Xue Za Zhi. 2018;98(14):1088–92. https://doi.org/10.3760/cmajissn0376-2491201814008.
Li J, Zhang YP, Kirsner RS. Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc Res Tech. 2003;60(1):107–14.
Acknowledgments
This study was supported by the Hamadan University of Medical Sciences (9804042566).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Monsef, F., Artimani, T., Alizadeh, Z. et al. Comparison of the regenerative effects of bone marrow/adipose-derived stem cells in the Asherman model following local or systemic administration. J Assist Reprod Genet 37, 1861–1868 (2020). https://doi.org/10.1007/s10815-020-01856-w
Received:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1007/s10815-020-01856-w
Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.
My notes (saved in your browser only)
Ask this paper
Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works
MeSH descriptors
Citation neighborhood (sparse)
Too few in-corpus citations on either side for a chart; here are the lists.
Cited by (1)
Cited by (1)
Source provenance
- europepmc
- last seen: 2026-06-19T06:14:56.452680+00:00
- pubmed
- last seen: 2026-05-13T22:21:59.141895+00:00
- unpaywall
- last seen: 2026-05-14T19:30:52.867331+00:00
License: public-domain-us
· commercial use OK
· attribution required
Courtesy of the U.S. National Library of Medicine
Courtesy of the U.S. National Library of Medicine