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Adipose-derived stem cells transplantation improves endometrial injury repair

Published online by Cambridge University Press:  27 August 2019

Xiaowen Shao
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Guihai Ai
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Lian Wang
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Jinlong Qin
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Yue Li
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Huici Jiang
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Tingting Zhang
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Linlin Zhou
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Zhengliang Gao
Affiliation:
Lifeng Institute of Regenerative Medicine, Tongji University, Shanghai, 200092, China
Jiajing Cheng
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
Zhongping Cheng*
Affiliation:
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
*
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: [email protected]

Summary

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.

Type
Research Article
Copyright
© Cambridge University Press 2019 

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Footnotes

*

These authors contributed equally to this work.

References

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.CrossRefGoogle ScholarPubMed
Achache, H and Revel, A (2006) Endometrial receptivity markers, the journey to successful embryo implantation. Human Reprod Update 12, 731–46.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Deans, R and Abbott, J (2010) Review of intrauterine adhesions. J Minim Invasive Gynecol 17, 555–69.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Frölich, K, Hagen, R and Kleinsasser, N (2014) Adipose-derived stromal cells (ASC) – basics and therapeutic approaches in otorhinolaryngology. Laryngorhinootologie 93, 369–80.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Gomillion, CT and Burg, KJ (2006) Stem cells and adipose tissue engineering. Biomaterials 27, 6052–63.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Gurtner, GC, Werner, S, Barrandon, Y and Longaker, MT (2008) Wound repair and regeneration. Nature 453, 314–21.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Kokai, LE, Marra, K and Rubin, JP (2014) Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Transl Res 163, 399408.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Liu, G and Chen, X (2018) Isolating and characterizing adipose-derived stem cells. Methods Mol Biol 1842, 193201.CrossRefGoogle ScholarPubMed
March, CM (2011a) Asherman’s syndrome. Semin Reprod Med 29, 8394.CrossRefGoogle ScholarPubMed
March, CM (2011b) Management of Asherman’s syndrome. Reprod Biomed Online 23, 6376.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Mizuno, H (2013) Adipose-derived stem cells for regenerative medicine in the field of plastic and reconstructive surgery. J Oral Biosci 55, 132–6.CrossRefGoogle Scholar
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.CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Petit-Zeman, S (2001) Regenerative medicine. Nat Biotechnol 19, 201–6.CrossRefGoogle ScholarPubMed
Ramakrishna, V, Janardhan, PB and Sudarsanareddy, L (2011) Stem cells and regenerative medicine a review. Ann Rev Res Biol 1, 79110.Google Scholar
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.CrossRefGoogle ScholarPubMed
Schenker, JG and Margalioth, EJ (1982) Intrauterine adhesions: an updated appraisal. Fertil Steril 37, 593610.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Tiscornia, G, Singer, O and Verma, IM (2006) Production and purification of lentiviral vectors. Nat Protoc 1, 241–5.CrossRefGoogle ScholarPubMed
Tobita, M, Orbay, H and Mizuno, H (2011) Adipose-derived stem cells: current findings and future perspectives. Discov Med 11, 160–70.Google ScholarPubMed
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.CrossRefGoogle Scholar
Yu, D, Wong, YM, Cheong, Y, Xia, E and Li, TC (2008) Asherman syndrome – one century later. Fertil Steril 89, 759–79.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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