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Int. J. Mol. Sci. 2014, 15(8), 13151-13165;

Potential Spermatogenesis Recovery with Bone Marrow Mesenchymal Stem Cells in an Azoospermic Rat Model

Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, 391 Technology Way, Winston-Salem, NC 27101, USA
Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China
Authors to whom correspondence should be addressed.
Received: 15 June 2014 / Revised: 15 July 2014 / Accepted: 16 July 2014 / Published: 24 July 2014
(This article belongs to the Special Issue Molecular Research in Urology 2014)
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Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit) were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy. View Full-Text
Keywords: mesenchymal stem cell; germ cell; spermatogonial stem cell; transplantation; differentiation mesenchymal stem cell; germ cell; spermatogonial stem cell; transplantation; differentiation

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Zhang, D.; Liu, X.; Peng, J.; He, D.; Lin, T.; Zhu, J.; Li, X.; Zhang, Y.; Wei, G. Potential Spermatogenesis Recovery with Bone Marrow Mesenchymal Stem Cells in an Azoospermic Rat Model. Int. J. Mol. Sci. 2014, 15, 13151-13165.

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