New Fertility Preserving Option for Male Cancer Survivors

描述（由申请人提供）：生精干细胞（ssc）维持出生后睾丸中的精子发生。这些成体组织干细胞可以提供一种基于细胞的治疗方法，用于治疗有时由化疗或放射治疗（例如，用于癌症或骨髓移植之前）引起的不孕症。理论上，SSCs可以在毒性治疗前分离并冷冻保存，然后在治疗完成和/或治愈后重新引入患者的睾丸。因此，通过自体ssc移植，男性幸存者有可能恢复自然生育能力并成为自己遗传后代的父亲。这种方法的原理证明已经在小鼠、大鼠和山羊身上得到了验证。此外，我们最近开发了一种非人类灵长类动物模型，该模型具有高剂量化疗导致的长期不育，这将使我们能够将这些想法转移到与人类生理学更相关的物种上。在哺乳动物中，精子发生是一个高度保守的过程，因此人们很容易推测分离、冷冻保存和移植SSCs的技术最终可以应用于人类。然而，这需要实验来证实。在人体组织中，研究SSC移植的一些关键的可行性和安全性问题有三个特定的目的。

DESCRIPTION (provided by applicant): Spermatogonial stem cells (SSCs) maintain spermatogenesis in the postnatal testis. These adult tissue stem cells may provide a cell-based therapy for treating infertility that sometimes results from chemotherapy or radiation treatments (e.g., for cancer or prior to bone marrow transplantation). Theoretically, SSCs can be isolated and cryopreserved prior to the toxic therapy and then reintroduced into the testes of the patient upon completion of treatment and/or cure. Thus, through autologous transplantation of SSCs, it may be possible for male survivors to recover natural fertility and father their own genetic children. The proof-in-principle for this approach is already established mice, rats and goats. In addition, we recently developed a nonhuman primate model with long-term infertility secondary to high dose chemotherapy that will allow us to transfer these ideas to a species with greater relevance to human physiology. Spermatogenesis is a highly conserved process in mammals, so it is tempting to speculate that techniques to isolate, cryopreserve and transplant SSCs can eventually be translated to humans. However, this needs to be confirmed experimentally. Three specific aims are designed to examine, in human tissues, some of the critical feasibility and safety issues associated with SSC transplantation. PUBLIC HEALTH RELEVANCE: Chemotherapy and radiation treatments for cancer can cause permanent infertility. Spermatogonial stem cell (SSC) transplantation is an experimental procedure that may offer fertile hope to cancer survivors. Critical feasibility and safety issues must be addressed before this new fertility preserving technology can be translated to the clinic. This application will provide initial insights about stem cell activity in normal human testis tissues and optimize techniques for human SSC isolation, enrichment and cryopreservation.