Ice-free cryopreservation of whole pediatric testes for autologous banking and replantation.

整个儿科睾丸的无冰冷冻保存用于自体储存和再植。

基本信息

批准号：
9919065
负责人：
Kelvin G.M. Brockbank
金额：
$ 30万
依托单位：
TISSUE TESTING TECHNOLOGIES, LLC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-15 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9919065
关键词：
Achievement Address Adolescent Adult Age AlamarBlue Animals Antioxidants Aplastic Anemia Apoptosis Apoptotic Applications Grants Autoimmune Diseases Autologous Autologous Transplantation Autopsy Back Benign Biological Assay Biopsy Birth Blood Vessel Tissue Breeding Cancer Patient Cancer Survivor Cell Survival Cells Characteristics Child Childhood Chronic Childhood Arthritis Clinic Complex Cooley&apos s anemia Cryopreservation Cryopreserved Cell Cytotoxic Chemotherapy Development Diagnosis Dimethyl Sulfoxide Dissection Dysmyelopoietic Syndromes Equilibrium Evaluation Exposure to Failure Fanconi&apos s Anemia Feasibility Studies Female Fertility Fertilization Fertilization in Vitro Fibrosis Formulation Frequencies Future Genetic Germ Cells Germ Lines Heart Valves Heating Hematological Disease High Dose Chemotherapy Histologic Histology Hormonal Hormones Human Ice Immune In Vitro Infertility Injury Interview Klinefelter&apos s Syndrome Lead Letters Libido Licensing Life Macaca mulatta Magnetism Maintenance Male Infertility Malignant Neoplasms Metals Methods Modeling Nitrogen Non-Malignant Oocytes Operative Surgical Procedures Outcome Parents Patients Phase Pre-implantation Embryo Development Pregnancy Production Propylene Glycols Protocols documentation Puberty Public Health Radiation therapy Rattus Reproductive Medicine Rewarming Rhesus Sales Sampling Scrotum Services Sex Functioning Sickle Cell Anemia Skin Small Business Innovation Research Grant Spermatogenesis Stains Structure Sucrose Surgeon Surgical Replantation Systemic Lupus Erythematosus Systemic Scleroderma Technology Testicular Tissue Testing Testis Testosterone Therapeutic immunosuppression Time Tissue Banks Tissue Viability Tissues Transplantation Trehalose base boys cancer diagnosis cancer therapy chemotherapy childhood cancer survivor commercialization cytopenia cytotoxic cytotoxicity formamide implantation improved innovation male nanoparticle nanowarming novel prepuberty preservation radio frequency repaired reproductive reproductive organ restoration sperm cell stem cells vapor ward young adult

项目摘要

Thousands of young males under the age of 20 are diagnosed with cancer each year. The overall cure rates of these cancer patients are approaching 80%; therefore, the number of childhood cancer survivors is increasing over time. It is well documented that cancer treatments may result in temporary, long-term, or permanent gonadal failure in male cancer survivors. Certain benign hematological disorders, such as myelodysplasia, sickle cell disease, aplastic anemia, thalassemia major, and Fanconi anemia, and severe autoimmune diseases unresponsive to immunosuppressive therapy, such as juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, systemic sclerosis and immune cytopenias, necessitate administration of high dose chemotherapy that may also impact testicles. In immature boys, in particular, storing testicular tissue prior to such cytotoxic treatments for future replantation could be an option. This proposal specifically addresses cryopreservation of pediatric testes. This male reproductive organ is contained within the scrotum, and is responsible for the production of sperm and the male hormone, testosterone that is pivotal for the maintenance of male sexual characteristics. As such, injury to the testes can render a young male infertile and needing administration of exogenous testosterone. Klinefelter’s syndrome patients would also benefit. Klinefelter’s syndrome the most common (1:500 new male born) genetic reason for male infertility, suffer from progressive germ cell loss and testis fibrosis with onset of puberty. We propose to remedy this by cryopreservation of testes that can be used for restoration of sexual function, fertility and hormonal balance in males before they are damaged. A single testis from each patient would be cryopreserved. This would permit either replantation of the patient’s intact testis, implantation of viable spermatogonial stem cells in the remaining testis, or ectopic implantation of functional spermatogonial stem cells. Each strategy would be capable of completing spermatogenesis and provide testosterone in a regulated way. We propose a novel innovative approach using ice-free vitrification to cryopreserve pediatric testes employing a young rat model. No animals will be sacrificed because we are using heterozygous and wild type culls from breeding colonies post-mortem. In this Phase I SBIR proposal in vitro methods and histology will be used to assess outcomes in three specific aims. Feasibility for progression to a Phase II SBIR grant proposal will be demonstrated by achievement of >80% cell viability by 3 methods and <20% apoptotic cells after 3 months of storage in vapor phase nitrogen. We have already assembled a world-class team of experts in surgery and reproductive medicine to guide the Company in Phase II and Phase III commercialization efforts.

每年有数千名 20 岁以下的年轻男性被诊断出患有癌症，这些癌症患者的总体治愈率接近 80%；因此，随着时间的推移，癌症治疗可能会导致儿童癌症幸存者的数量不断增加。导致男性癌症幸存者暂时、长期或永久性性腺功能衰竭，以及严重的骨髓增生异常、镰状细胞病、再生障碍性贫血、重型地中海贫血和范可尼贫血。对免疫抑制治疗无反应的自身免疫性疾病，例如青少年特发性关节炎、青少年系统性红斑狼疮、系统性硬化症和免疫性血细胞减少症，需要给予高剂量化疗，这也可能影响未成熟男孩的睾丸，尤其是在使用细胞毒性药物之前储存睾丸组织。该提案专门针对儿童睾丸的冷冻保存，该男性生殖器官包含在体内。阴囊负责产生精子和雄性激素，睾酮对于维持男性性特征至关重要，因此，睾丸损伤可能导致年轻男性不育，需要服用外源性睾酮。克兰费尔特氏综合症是男性不育的最常见（1:500 新生儿）遗传原因，随着青春期的到来，患有进行性生殖细胞丧失和睾丸纤维化。通过冷冻保存可用于在男性受损之前恢复性功能、生育能力和荷尔蒙平衡的测试来解决这个问题，这将允许重新移植患者完整的睾丸，或植入睾丸。我们建议，在剩余的睾丸中存活的精原干细胞，或功能性精原干细胞的异位植入都能够完成精子发生并以受监管的方式提供睾酮。一种新颖的创新方法，使用无冰玻璃化冷冻保存采用幼年大鼠模型的儿科测试，因为我们在这一阶段的 SBIR 体外方法中使用来自繁殖群体的杂合和野生型剔除。组织学将用于评估三个具体目标的结果进展到 II 期 SBIR 资助提案的可行性将通过 3 种方法实现 >80% 的细胞活力和 <20% 来证明。我们已经组建了世界一流的外科和生殖医学专家团队来指导公司进行二期和三期商业化工作。