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Int J Med Sci 2012; 9(7):592-602. doi:10.7150/ijms.4841

Research Paper

CD44+/CD105+ Human Amniotic Fluid Mesenchymal Stem Cells Survive and Proliferate in the Ovary Long-Term in a Mouse Model of Chemotherapy-Induced Premature Ovarian Failure

Te Liu1,2,5✉, Yongyi Huang5, Lihe Guo3,5, Weiwei Cheng2, Gang Zou4

1. Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, China;
2. International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai 200030, China;
3. Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
4. Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China;
5. Sino-America United Stem Cell Research Center, Shanghai 200333, China.

Abstract

Objectives: Stem cell transplantation has been reported to rescue ovarian function in a preclinical mouse model of chemotherapy-induced premature ovarian failure (POF); however, maintaining the survival and self-renewal of transplanted seed cells in ovarian tissues over the long-term remains a troublesome issue. In this study we aimed to determine whether the CD44+/CD105+ human amniotic fluid cell (HuAFCs) subpopulation represent potential seed cells for stem cell transplantation treatments in POF. Materials and methods: The CD44+/CD105+ subpopulation were isolated from HuAFCs, cultured in vitro, and injected into a cyclophosphamide-induced mouse model of POF. Results: Under continuous subculture in vitro, CD44+/CD105+ cells proliferated rapidly and expressed high levels of the proliferative markers Ki67 and survivin, as well as high levels of a number of mesenchymal stem cell biomarkers. Moreover, when red fluorescence protein (RFP)-transduced CD44+/CD105+ HuAFCs were transplanted into the ovaries of POF mice, the cells could be detected by fluorescence microscopy up to three weeks after injection. Furthermore, the BrdUrd incorporation assay and immunofluorescent staining demonstrated that CD44+/CD105+ HuAFCs underwent normal cycles of cell proliferation and self-renewal in the ovarian tissues of POF mice over the long-term. Conclusions: The mesenchymal stem cell properties and long-term in vivo survival of CD44+/CD105+ HuAFCs make them ideal seed cells for stem cell transplantation to treat POF.

Keywords: Mouse premature ovarian failure model, cell transplantation, human amniotic fluid cells, mesenchymal stem cell like cells, long-term survival, proliferation.

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How to cite this article:
Liu T, Huang Y, Guo L, Cheng W, Zou G. CD44+/CD105+ Human Amniotic Fluid Mesenchymal Stem Cells Survive and Proliferate in the Ovary Long-Term in a Mouse Model of Chemotherapy-Induced Premature Ovarian Failure. Int J Med Sci 2012; 9(7):592-602. doi:10.7150/ijms.4841. Available from http://www.medsci.org/v09p0592.htm