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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：
10569553
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/10569553
关键词：
Acceleration Affect Allogenic Allografting Autologous Transplantation Biocompatible Materials Bone Marrow Transplantation Cancer Survivor Cardiovascular Diseases Cells Chemotherapy and/or radiation Child Circulation Complication Data Devices Diabetes Mellitus Diffusion Disease remission Dose Encapsulated Endocrine Engineering Equilibrium Estrogen deficiency 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 Immunocompetent Immunocompromised Host Immunologic Sensitization Immunologics Immunosuppression Implant Investigation Isoantibodies Laboratory mice Life Longevity Malignant Childhood Neoplasm Memory Modeling Modernization Mus Muscular Atrophy Nature Obesity Osteopenia Ovarian Ovarian Tissue Ovarian hormone Ovarian tissue cryopreservation Pattern Periodicity Physiological Physiology Progesterone Property Puberty Recurrent Malignant Neoplasm Research Risk Rodent Skin graft Sterility Stimulus Survival Rate Testing Tissue Donors Tissue Grafts Tissues Transplantation Treatment-related toxicity United States Xenograft procedure anticancer treatment 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 meter 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.

项目概要卵巢早衰（POI）是抗癌治疗的常见并发症，例如如化疗和骨髓移植，由于治疗毒性。在女性癌症中幸存者 POI 会导致不育和卵巢内分泌功能丧失，进而导致过早骨质减少、肌肉萎缩和加速心血管疾病。这些长持久影响是显着的，特别是对于进入青春期的年轻女孩。长期目标是我们的研究是开发一种方法来恢复年轻女性的卵巢内分泌功能 POI 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充分表征的生物材料并针对卵巢独特生理学进行调整的胶囊组织。事实证明，我们的方法在使用啮齿动物供体组织的小鼠中是成功的，但人类卵巢组织中基质和卵泡的比例、大小存在显着差异人类卵泡达到成熟以及休眠和激活卵泡之间的平衡啮齿动物和人类之间的关系需要使用人类卵巢组织进行进一步研究。如果如果成功的话，这种方法将为恢复卵巢提供一种临床相关且未经探索的工具 POI 年轻女性的内分泌功能。