Engineering an immuno-isolating hydrogel for restoring ovarian endocrine function

设计用于恢复卵巢内分泌功能的免疫隔离水凝胶

基本信息

批准号：
10378486
负责人：
Ariella Shikanov
金额：
$ 40.08万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10378486
关键词：
Affect Allogenic Allografting Autologous Transplantation Biocompatible Materials Blood Circulation Bone Marrow Transplantation Cancer Survivor Cardiovascular Diseases Cells Chemotherapy and/or radiation Child Complication Data Devices Diabetes Mellitus Diffusion Disease remission Dose Encapsulated Endocrine Engineering Equilibrium Estrogens Estrus Event Exposure to Face Female Female Adolescents Fertility Follicle Stimulating Hormone Formulation Freezing Funding Goals Growth Health Hematologic Neoplasms Homologous Transplantation Hormonal Hormone imbalance Hormone replacement therapy Human Hydrogels Immune Immune response Immunization Immunocompetent Immunocompromised Host Immunologics Immunosuppression Implant Investigation Isoantibodies Laboratory mice Life Longevity Malignant Childhood Neoplasm Memory Mind Modeling Modernization Mus Muscular Atrophy Nature Obesity Osteopenia Ovarian Ovarian Tissue Ovarian hormone Ovarian tissue cryopreservation Pattern Periodicity Physiological Physiology Progesterone Property Puberty Research Risk Rodent Skin graft Sterility Stimulus Survival Rate Testing Tissue Donors Tissue Grafts Tissues Transplantation Treatment-related toxicity United States Wasting Syndrome Xenograft procedure anticancer treatment base cancer cell cancer recurrence cancer risk cancer therapy capsule chemotherapy clinical translation clinically relevant cognitive development cohort cytotoxic design ethylene glycol folliculogenesis girls graft function human model human tissue implantation improved in vivo innovation isoimmunity loss of function malignant breast neoplasm millimeter negative affect novel premature preservation prevent primary ovarian insufficiency response standard of care stem thrombotic tool young woman

项目摘要

Project Summary Premature ovarian insufficiency (POI) is a common complication of anticancer treatments, such as chemotherapy and bone marrow transplantation, due to treatment toxicity. In female cancer survivors POI causes sterility, and loss of the ovarian endocrine function, which in turn results in premature osteopenia, muscle wasting, and accelerated cardiovascular disease. These long- lasting effects are significant, particularly for young girls reaching puberty. The long-term goal of our research is to develop a means to restore ovarian endocrine function in young women with POI by utilizing allogeneic transplantation of ovarian tissue. We designed an immuno-isolating capsule based on well-characterized biomaterials and tuned to the unique physiology of ovarian tissue. Our approach proved to be successful in mice using donor tissue from rodents, yet the significant differences in ratio between stroma and follicles in human ovarian tissue, size that human follicles reach at maturity and the balance between dormant and activated follicles between rodents and humans require further investigation using human ovarian tissue. If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian endocrine function in young women with POI.

项目摘要早产卵巢不足（POI）是抗癌治疗的常见并发症，例如由于治疗毒性，作为化学疗法和骨髓移植。在女性癌症中幸存者POI会导致不育和卵巢内分泌功能的丧失，从而导致过早的骨质减少，肌肉浪费和加速心血管疾病。这些很长的持久的影响很重要，特别是对于青春期的年轻女孩而言。长期目标我们的研究是开发一种方法来恢复患有的年轻女性的卵巢内分泌功能通过利用卵巢组织的同种异体移植。我们设计了一种免疫隔离基于特征良好的生物材料的胶囊，并调整为卵巢独特的生理学组织。我们的方法被证明是使用啮齿动物的供体组织在小鼠中成功的，但是人卵巢组织中基质和卵泡之间的比率显着差异，大小人卵泡到期时达到和休眠和活化卵泡之间的平衡啮齿动物和人之间需要使用人类卵巢组织进行进一步研究。如果成功，这种方法将提供临床上相关且未开发的工具来恢复卵巢 POI的年轻女性的内分泌功能。