New Fertility Preserving Option for Male Cancer Survivors

男性癌症幸存者保留生育能力的新选择

基本信息

批准号：
8068238
负责人：
Kyle Edwin Orwig
金额：
$ 18.57万
依托单位：
MAGEE-WOMEN'S RES INST AND FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8068238
关键词：
Activities of Daily Living Address Adult Animal Model Autologous Transplantation Back Biological Assay Biological Preservation Biology Bone Marrow Transplantation Cancer Survivor Cancer Survivorship Cancer cell line Canis familiaris Cell Separation Cell Therapy Cell Transplants Cell surface Cells Child Childhood Clinic Collaborations Cryopreservation Development Disease Ensure Environment Ethics Excision Exploratory/Developmental Grant Fathers Fertility Flow Cytometry Fluorescence-Activated Cell Sorting Freezing Funding Genetic Goat Health Health Sciences High Dose Chemotherapy Human Infertility Institutional Review Boards Knowledge Lead Letters Macaca mulatta Magnetism Malignant Neoplasms Mammals Methods Modeling Monkeys Mus Natural Fertility Nude Mice Organ Donor Parents Patients Pediatric Oncologist Phenotype Physiology Pre-Clinical Model Primates Procedures Process Publications Quality of life Radiation Rattus Reproductive Endocrinology Research Institute Research Project Grants Risk Safety Secondary to Sorting - Cell Movement Spermatogenesis Staging Stem cell transplant Stem cells Survival Rate Survivors Techniques Technology Testicular Tissue Testis Tissue Banking Tissue Banks Tissues Translating Transplantation United States National Institutes of Health Universities Urologist Woman Xenograft procedure boys cancer cell cancer therapy chemotherapy design human tissue improved insight male medical schools medical specialties meetings men nonhuman primate novel oncology postnatal pre-clinical preclinical study programs public health relevance response technology development tool

项目摘要

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.

描述（由申请人提供）：精子干细胞（SSC）在产后睾丸中保持精子发生。这些成年组织干细胞可能会提供基于细胞的治疗疗法，以治疗不孕症，有时是由化学疗法或放射治疗（例如癌症或骨髓移植之前）引起的。从理论上讲，可以在有毒疗法之前分离和冷冻保存SSC，然后在完成治疗和/或治愈后重新引入患者的睾丸。因此，通过自体移植SSC，男性幸存者可能有可能恢复自然的生育能力并父亲自己的遗传儿童。这种方法的校对已经是已经建立的小鼠，老鼠和山羊。此外，我们最近开发了一种非人类的灵长类动物模型，其长期不孕症继发于高剂量化疗，这将使我们能够将这些思想转移到与人类生理学更相关的物种中。精子发生是哺乳动物中高度保守的过程，因此很容易推测分离，冷冻水果和移植SSC的技术最终可以转化为人类。但是，这需要通过实验确认。在人体组织中，设计了三个特定的目标，这些目标是与SSC移植相关的一些关键可行性和安全问题。公共卫生相关性：癌症的化学疗法和放射治疗可能会导致永久性不育症。精子干细胞（SSC）移植是一种实验性程序，可能为癌症幸存者提供肥沃的希望。在将这种新的生育能力保存技术转化为诊所之前，必须解决关键的可行性和安全问题。该应用将提供有关正常人睾丸组织中干细胞活性的初始见解，并优化人类SSC隔离，富集和冷冻保存的技术。