来源于脐带间充质干细胞的分泌因子对化疗引起的生精细胞损伤的修复作用

Spermatogenic dysfunction caused by chemotherapy is important for male infertility. Besides assisted reproductive technology, searching a therapeutic strategy for repairing spermatogenic cells and for affecting spermatogenesis micro-environment after chemotherapy and reducing the damage of chemotherapy drugs to patients with spermatogenic function become research hotspots in andrology. The Applicant’s preliminary work for transplanting umbilical cord mesenchymal stem cells (HUCMSCs) into the mice model of azoospermia,supports the increased expression of germline specific genes. HUCMSCs may promote the recovery of spermatogenesis. In this study, we further isolate the secreted factors from HUCMSCs, and then perform in vivo transplantation experiments and interacting with spermatogenic cell in vitro, respectively. And we investigate the paracrine effect of HUCMSCs. We try to verify whether secretory factors can activate PI3K/Akt/mTOR signaling pathway and alleviate the damage of spermatogenic cells induced by busulfan. By this verification, we can clarify the role of HUCMSCs secreted factors in the promotion of spermatogenesis. The goal of this study is to find a simple, safe, and effective MSCs based on cellular therapy. This study will provide a new strategy for the further exploration of the repair of spermatogenesis.

化疗引起的生精障碍是男性因素中引起不育的重要原因。在辅助生殖技术之外，寻找能够修复化疗后睾丸生精细胞和影响精子发生的“微环境”的治疗策略,有效减少化疗药物对患者生精功能的损害，成为男科生殖领域的研究热点。申请人前期研究将脐带间充质干细胞（HUCMSCs）移植入无精子症小鼠模型，证实生殖细胞特异性的基因表达上调，从而表明HUCMSCs对睾丸生精功能的恢复可能具有促进作用。本课题通过进一步分离HUCMSCs来源的分泌因子，分别进行体内移植实验，体外与生精细胞相互作用实验，探索HUCMSCs的旁分泌功能。验证分泌因子能否通过激活PI3K/Akt/mTOR信号通路，缓解白消安引起的生精细胞损伤，从而阐明来源于HUCMSCs的分泌因子对生精功能的促进作用。该项研究同时是寻找一种操作简单、安全有效的基于MSCs的非細胞疗法，为进一步探索生精损伤的修复提供了新策略。