Preserving Male Fertility After Cancer Therapy

癌症治疗后保持男性生育能力

• 批准号: 8878315
• 负责人: Kyle Edwin Orwig
• 金额: $ 140.72万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8878315
• 关键词: Adolescent; Adoption; Adult; Affect; Age; American; American Society of Clinical Oncology; Anatomy; Animal Model; Animals; Area; Autoimmune Diseases; Autologous Transplantation; Behavior Therapy; Biological; Biological Preservation; Blood; Bone Marrow Transplantation; Cancer Patient; Cancer Survivor; Cell Therapy; Cell Transplantation; Chemicals; Child; Child health care; Childhood; Childhood Cancer Survivor Study; Clinic; Clinical Data; Communication; Country; Cryopreservation; Cytotoxic Chemotherapy; Data; Data Reporting; Development; Diagnosis; Disease; Distress; Ethics Committees; Exposure to; Family; Fathers; Fertility; Freezing; Future; Genetic; Germ Cells; Gonadal structure; Health; Hematopoietic stem cells; High Dose Chemotherapy; Hormonal; Hormones; Human; Human Cell Line; Human Development; Immune; Incidence; Individual; Infertility; Institutes; Knowledge; Lead; Macaca mulatta; Male Infertility; Malignant Childhood Neoplasm; Malignant Neoplasms; Methods; Modeling; Monkeys; Mus; National Institute of Child Health and Human Development; Natural regeneration; Non-Malignant; Organ Culture Techniques; Pancytopenia; Parents; Patients; Physiology; Pre-Clinical Model; Publishing; Quality of life; Radiation; Radiation therapy; Recommendation; Reporting; Reproduction; Reproductive Medicine; Reproductive Technology; Research; Research Personnel; Resources; Risk; Safety; Sampling; Science; Seminal fluid; Site; Societies; Specimen; Spermatogenesis; Spermatogonia; Stem cell transplant; Stem cells; Sterility; Sum; Survivors; Testicular Tissue; Testis; Tissue Grafts; Tissue Preservation; Tissues; Translating; Translations; Transplantation; United States; United States National Institutes of Health; Whole-Body Irradiation; base; boys; cancer therapy; chemotherapy; childhood cancer survivor; germline stem cells; high risk; induced pluripotent stem cell; interest; irradiation; male; men; novel; patient population; pre-clinical; preclinical study; prepuberty; programs; psychologic; reproductive; safety testing; sperm cell; statistics; stem cell biology; stem cell technology; stem cell therapy; symposium

DESCRIPTION (provided by applicant): Chemotherapy and radiation treatments for cancer or other conditions can cause prolonged or permanent infertility. This is a significant human health concern because over 75,000 people under the age of 40 In the United States are diagnosed with cancer each year and most are cured. Adult men have the option to cryopreserve semen with sperm prior to gonadotoxic. This option is not available to prepubertal boys or adult male survivors who did not save a semen sample before treatment. For these patients, there are several stem cell technologies in the research pipeline that may preserve or restore fertility. Thi program project will generate pre-clinical radiation- and chemotherapy-induced models of male infertility in rhesus macaques that are relevant to human testis anatomy, physiology and pubertal development. The overall objective is to examine the long-term impacts of pre-pubertal chemotherapy and radiation exposure on stem cells and spermatogenesis and determine the potential of stem cell therapies to preserve and/or restore fertility. Proiect I (OnA/ig) will evalate the potential of spermatogonia stem cell (SSC) transplantation and testicular tissue grafting or organ culture to regenerate spermatogenesis and/or produce functional sperm in monkeys treated with gonadotoxic agents during childhood. Proiect II (Clark/Byrne) will derive animal-specific induced pluripotent stem cells (IPSCs) and differentiate them into transplantable germline stem cells with autologous transplantation into chemo- and radiation-treated recipients. Proiect III (Meistrich/Shettv) will develop novel hormone suppression strategies to stimulate spermatogenesis from endogenous and/or transplanted SSCs after exposure to gonadotoxic agents. The Administrative Core A will coordinate communication and collegial interaction between project sites, transfer of biological specimens and data and report progress to NIH. Transplant Core B will provide high quality disease free rhesus macaques of the appropriate ages, generate irradiated and chemotherapy-treated models of male infertility and provide the expertise for germ cell transplantation into mice and monkeys. Each project site brings unique knowledge, expertise and resources to the program that are not available in composite at any ofthe individual sites or anywhere else in the country. Collectively, the project leaders will generate a substantial body of pre-clinical data on the feasibility of stem cell-based methods for preserving and/or restoring fertility of patients receiving gonadotoxic therapies.

描述（由申请人提供）：癌症或其他疾病的化学疗法和放射治疗可能会导致长时间或永久性不育症。这是一个重大的人类健康问题，因为美国每年有75,000人40岁以下的人被诊断出患有癌症，大多数人都被治愈。成年男性可以选择在促性腺毒性之前用精子冷冻reservere精液。这种选择不适合在治疗前没有保存精液样本的青春期前男孩或成年男性幸存者。对于这些患者，研究管道中有几种干细胞技术可以保留或恢复生育能力。 THI计划项目将产生与人类睾丸解剖学，生理学和青春期发展有关的恒河猕猴中的临床前辐射和化学疗法诱导的男性不育症模型。总体目的是检查前化学疗法和放射线对干细胞和精子发生的长期影响，并确定干细胞疗法保留和/或恢复生育能力的潜力。 Pro I（ONA/IG）将评估精子性干细胞（SSC）移植和睾丸组织移植或器官培养的潜力，以再生精子发生和/或在童年期间用性腺毒性药物治疗的猴子中产生功能精子。 Proiect II（Clark/Byrne）将推导动物特异性诱导的多能干细胞（IPSC），并将其自体移植到化学和放射治疗的受体中分化为可移植的种系干细胞。 Proiect III（Meistrich/SHETTV）将开发新型的激素抑制策略，以刺激暴露于性腺毒性剂后内源性和/或移植的SSC的精子发生。行政核心A将协调项目站点之间的通信和合作互动，生物标本和数据的转移，并将进度报告给NIH。移植核心B将提供适当年龄的高质量恒河猕猴，产生辐照和化学疗法治疗的男性不育症模型，并为生殖细胞移植到小鼠和猴子中提供专业知识。每个项目站点都会为计划带来独特的知识，专业知识和资源，这些知识，专业知识和资源在任何单个站点或该国其他任何地方都无法提供。总体而言，项目领导者将生成大量的临床前数据，以了解基于干细胞的方法来保存和/或恢复接受性腺毒性疗法的患者的生育能力的可行性。