title: Potential spermatogenesis recovery with bone marrow mesenchymal stem cells in an azoospermic rat model.
abstract: 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.
authors: Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China. dzdy199@126.com.
authors: Deying
authors: D
authors: Zhang
authors: Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China. liux_0217@163.com.
authors: Xing
authors: X
authors: Liu
authors: Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China. pink-floyd@foxmail.com.
authors: Jinpu
authors: J
authors: Peng
authors: Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China. dw.he@163.com.
authors: Dawei
authors: D
authors: He
authors: Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China. lintao272@aliyun.com.
authors: Tao
authors: T
authors: Lin
authors: 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. jingzhu@cqmu.edu.cn.
authors: Jing
authors: J
authors: Zhu
authors: Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China. lixuliang2003@aliyun.com.
authors: Xuliang
authors: X
authors: Li
authors: Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China. yzhang@wakehealth.edu.
authors: Yuanyuan
authors: Y
authors: Zhang
authors: Department of Urology, Children's Hospital of Chongqing Medical University, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China. ghwei@cqmu.edu.cn.
authors: Guanghui
authors: G
authors: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D053713:Azoospermia / Q000139:chemically induced / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology*; D002066:Busulfan / Q000633:toxicity; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013093:Spermatogonia / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D012097:Repressor Proteins; D053487:DEAD-box RNA Helicases; D002066:Busulfan