Skip to main content Accessibility help

Adipose-derived stem cells transplantation improves endometrial injury repair

  • Xiaowen Shao (a1), Guihai Ai (a1), Lian Wang (a1), Jinlong Qin (a1), Yue Li (a1), Huici Jiang (a1), Tingting Zhang (a1), Linlin Zhou (a1), Zhengliang Gao (a2), Jiajing Cheng (a1) and Zhongping Cheng (a1)...


Endometrial injury is an important cause of intrauterine adhesion (IUA), amenorrhea and infertility in women, with limited effective therapies. Recently, stem cells have been used in animal experiments to repair and improve injured endometrium. To date, our understanding of adipose-derived stem cells (ADSCs) in endometrial injury repair and their further therapeutic mechanisms is incomplete. Here, we examined the benefit of ADSCs in restoration of injured endometrium by applying a rat endometrial injury model. The results revealed by immunofluorescence showed that green fluorescent protein (GFP)-labelled ADSCs can differentiate into endometrial epithelial cells in vivo. At 30 days after ADSCs transplantation, injured endometrium was significantly improved, with increased microvessel density, endometrial thickness and glands when compared with the model group. Furthermore, the fertility of rats with injured endometrium in ADSCs group was improved and had a higher conception rate (60% vs 20%, P = 0.014) compared with the control phosphate-buffered saline (PBS) group. However, there was no difference in the control group compared with the sham group. In addition, expression levels of the oestrogen receptor Eα/β (ERα, ERβ) and progesterone receptor (PR) detected by western blot and enzyme-linked immunosorbent assay (ELISA) were higher in the ADSCs group than in the PBS group. Taken together, these results suggested that ADSC transplantation could improve endometrial injury as a novel therapy for IUA.


Corresponding author

Address for correspondence: Zhongping Cheng. Department of Gynecology and Obstetrics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, No. 301, Yan Chang Road, 200072, Shanghai, China. Tel: +86 21 66300588. E-mail:


Hide All

These authors contributed equally to this work.



Hide All
Abumaree, MH, Al Jumah, MA, Kalionis, B, Jawdat, D, Al Khaldi, A, Al Talabani, AA and Knawy, BA (2013) Phenotypic and functional characterization of mesenchymal stem cells from chorionic villi of human term placenta. Stem Cell Rev 9, 1631.
Achache, H and Revel, A (2006) Endometrial receptivity markers, the journey to successful embryo implantation. Human Reprod Update 12, 731–46.
Azizi, R, Aghebati-Maleki, L, Nouri, M, Marofi, F, Negargar, S and Yousefi, M (2018) Stem cell therapy in Asherman syndrome and thin endometrium: stem cell-based therapy. Biomed Pharmacother 102, 333–43.
Bacakova, L, Zarubova, J, Travnickova, M, Musilkova, J, Pajorova, J, Slepicka, P, Kasalkova, NS, Svorcik, V, Kolska, Z, Motarjemi, H and Molitor, M (2018) Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells – a review. Biotechnol Adv 36, 1111–26.
Campo, H, Cervello, I and Simon, C (2017) Bioengineering the uterus: an overview of recent advances and future perspectives in reproductive medicine. Annals Biomed Eng 45, 1710–7.
Cheung, HK, Han, TT, Marecak, DM, Watkins, JF, Amsden, BG and Flynn, LE (2014) Composite hydrogel scaffolds incorporating decellularized adipose tissue for soft tissue engineering with adipose-derived stem cells. Biomaterials 35, 1914–23.
Deans, R and Abbott, J (2010) Review of intrauterine adhesions. J Minim Invasive Gynecol 17, 555–69.
Ding, L, Li, X, Sun, H, Su, J, Lin, N, Péault, B, Song, T, Yang, J, Dai, J and Hu, Y (2014) Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus. Biomaterials 35, 4888–900.
Eto, H, Suga, H, Matsumoto, D, Inoue, K, Aoi, N, Kato, H, Araki, J and Yoshimura, K (2009) Characterization of structure and cellular components of aspirated and excised adipose tissue. Plast Reconstr Surg 124, 1087–97.
Frölich, K, Hagen, R and Kleinsasser, N (2014) Adipose-derived stromal cells (ASC) – basics and therapeutic approaches in otorhinolaryngology. Laryngorhinootologie 93, 369–80.
Gadelkarim, M, Abushouk, AI, Ghanem, E, Hamaad, AM, Saad, AM and Abdel-Daim, MM (2018) Adipose-derived stem cells: effectiveness and advances in delivery in diabetic wound healing. Biomed Pharmacother 107, 625–33.
Gomillion, CT and Burg, KJ (2006) Stem cells and adipose tissue engineering. Biomaterials 27, 6052–63.
Goulopoulou, S, Hannan, JL, Matsumoto, T and Webb, RC (2012) Pregnancy reduces RhoA/Rho kinase and protein kinase C signaling pathways downstream of thromboxane receptor activation in the rat uterine artery. Am J Physiol Heart Circ Physiol 302, H2477–88.
Gurtner, GC, Werner, S, Barrandon, Y and Longaker, MT (2008) Wound repair and regeneration. Nature 453, 314–21.
Hyodo, S, Matsubara, K, Kameda, K and Matsubara, Y (2011) Endometrial injury increases side population cells in the uterine endometrium: a decisive role of estrogen. Tohoku J Exp Med 224, 4755.
Johary, J, Xue, M, Zhu, X, Xu, D and Velu, PP (2014) Efficacy of estrogen therapy in patients with intrauterine adhesions: systematic review. J Minim Invasive Gynecol 21, 4454.
Kokai, LE, Marra, K and Rubin, JP (2014) Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Transl Res 163, 399408.
Kwon, DS, Gao, X, Liu, YB, Dulchavsky, DS, Danyluk, AL, Bansal, M, Chopp, M, McIntosh, K, Arbab, AS, Dulchavsky, SA and Gautam, SC (2008) Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats. Int Wound J 5, 453–63.
Liu, G and Chen, X (2018) Isolating and characterizing adipose-derived stem cells. Methods Mol Biol 1842, 193201.
March, CM (2011a) Asherman’s syndrome. Semin Reprod Med 29, 8394.
March, CM (2011b) Management of Asherman’s syndrome. Reprod Biomed Online 23, 6376.
Melief, SM, Zwaginga, JJ, Fibbe, WE and Roelofs, H (2013) Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts. Stem Cells Transl Med 2, 455–63.
Mizuno, H (2013) Adipose-derived stem cells for regenerative medicine in the field of plastic and reconstructive surgery. J Oral Biosci 55, 132–6.
Mohr, A and Zwacka, R (2018) The future of mesenchymal stem cell-based therapeutic approaches for cancer – from cells to ghosts. Cancer Lett 414, 239–49.
Nae, S, Bordeianu, I, Stăncioiu, AT and Antohi, N (2013) Human adipose-derived stem cells: definition, isolation, tissue-engineering applications. Rom J Morphol Embryol 54, 919–24.
Navone, SE, Pascucci, L, Dossena, M, Ferri, A, Invernici, G, Acerbi, F, Cristini, SES, Bedini, G, Tosetti, V, Ceserani, V, Bonomi, A, Pessina, A, Freddi, G, Alessandrino, A, Ceccarelli, P, Campanella, R, Marfia, G, Alessandri, G and Parati, EA (2014) Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice. Stem Cell Res Ther 5, 7.
Petit-Zeman, S (2001) Regenerative medicine. Nat Biotechnol 19, 201–6.
Ramakrishna, V, Janardhan, PB and Sudarsanareddy, L (2011) Stem cells and regenerative medicine a review. Ann Rev Res Biol 1, 79110.
Roy, KK, Negi, N, Subbaiah, M, Kumar, S, Sharma, JB and Singh, N (2014) Effectiveness of estrogen in the prevention of intrauterine adhesions after hysteroscopic septal resection: a prospective, randomized study. J Obstet Gynaecol Res 40, 1085–8.
Schenker, JG and Margalioth, EJ (1982) Intrauterine adhesions: an updated appraisal. Fertil Steril 37, 593610.
Shekkeris, AS, Jaiswal, PK and Khan, WS (2012) Clinical applications of mesenchymal stem cells in the treatment of fracture non-union and bone defects. Curr Stem Cell Res Ther 7, 127–33.
Si, Z, Wang, X, Sun, C, Kang, Y, Xua, J, Wang, X and Hui, Y (2019) Adipose-derived stem cells: sources, potency, and implications for regenerative therapies. Biomed Pharmacother 114, 108765.
Tiscornia, G, Singer, O and Verma, IM (2006) Production and purification of lentiviral vectors. Nat Protoc 1, 241–5.
Tobita, M, Orbay, H and Mizuno, H (2011) Adipose-derived stem cells: current findings and future perspectives. Discov Med 11, 160–70.
Urman, B, Mercan, R, Alatas, C, Balaban, B, Isiklar, A and Nuhoglu, A (2000) Low-dose aspirin does not increase implantation rates in patients undergoing intracytoplasmic sperm injection: a prospective randomized study. J Assist Reprod Gen 17, 586–90.
Yu, D, Wong, YM, Cheong, Y, Xia, E and Li, TC (2008) Asherman syndrome – one century later. Fertil Steril 89, 759–79.
Zhang, Y, Khan, D, Delling, J and Tobiasch, E (2012) Mechanisms underlying the osteo- and adipo-differentiation of human mesenchymal stem cells. Sci World J 2012, 793823.
Zhao, J, Zhang, Q, Wang, Y and Li, Y (2015) Uterine infusion with bone marrow mesenchymal stem cells improves endometrium thickness in a rat model of thin endometrium. Reprod Sci 22, 181–8.
Zhou, BO, Yue, R, Murphy, MM, Peyer, JG and Morrison, SJ (2014) Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell 15, 154–68.
Zhou, Z, Chen, Y, Zhang, H, Min, S, Yu, B, He, B and Jin, A (2013) Comparison of mesenchymal stromal cells from human bone marrow and adipose tissue for the treatment of spinal cord injury. Cytotherapy 15, 434–48.
Zuk, PA, Zhu, M, Mizuno, H, Huang, J, Futrell, JW, Katz, AJ, Bentham, P, Lorenz, HP and Hedrick, MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7, 211–28.
Zuk, PA, Zhu, M, Ashjian, P, De Ugarte, DA, Huang, JI, Mizuno, H, Alfonso, ZC, Fraser, JK, Bentham, P and Hedrick, MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13, 4279–95.


Type Description Title
Supplementary materials

Shao et al. supplementary material
Shao et al. supplementary material 1

 Word (19 KB)
19 KB

Adipose-derived stem cells transplantation improves endometrial injury repair

  • Xiaowen Shao (a1), Guihai Ai (a1), Lian Wang (a1), Jinlong Qin (a1), Yue Li (a1), Huici Jiang (a1), Tingting Zhang (a1), Linlin Zhou (a1), Zhengliang Gao (a2), Jiajing Cheng (a1) and Zhongping Cheng (a1)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed