New Fertility Preserving Option for Male Cancer Survivors

描述(申请人提供)：精原干细胞(SSCs)在出生后的睾丸中维持精子的发生。这些成人组织干细胞可以提供一种基于细胞的疗法，用于治疗有时由化疗或放射治疗(例如，癌症或骨髓移植之前)引起的不孕不育。理论上，SSCs可以在中毒治疗前被分离和冷冻保存，然后在治疗和/或治愈完成后重新注入患者的睾丸。因此，通过自体移植干细胞，男性幸存者有可能恢复自然生育能力，并成为自己基因孩子的父亲。这种方法的原则证据已经确定为小鼠、大鼠和山羊。此外，我们最近开发了一个非人类灵长类动物模型，该模型继发于高剂量化疗，继发于长期不孕，这将使我们能够将这些想法转移到与人类生理更相关的物种上。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的技术最终可以移植到人类身上。然而，这一点还需要实验来证实。在人体组织中，设计了三个特定的目标来检查与SSC移植相关的一些关键的可行性和安全性问题。 公共卫生相关性：癌症的化疗和放射治疗可能导致永久性不孕。精原干细胞(SSC)移植是一种实验程序，可能会给癌症幸存者带来希望。必须解决关键的可行性和安全性问题，然后才能将这项新的保留生育能力的技术转化到临床上。这一应用将提供有关正常人类睾丸组织中干细胞活性的初步见解，并优化人类SSC的分离、浓缩和冷冻保存技术。

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.