Isochoric Pressure Based Preservation of Ovarian Tissue

基于等容压的卵巢组织保存

• 批准号: 10392764
• 负责人: Bradley P Weegman
• 金额: $ 58.78万
• 依托单位: SYLVATICA BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10392764
• 关键词: Address; American; American Society of Clinical Oncology; Area; Autoimmune Diseases; Autologous; Autologous Transplantation; Biomedical Research; Blood Vessels; Bone Marrow; Cancer Survivor; Cell Volumes; Chemicals; Chemotherapy and/or radiation; Child; Childhood; Climacteric; Clinic; Clinical; Competence; Complement; Complex; Continuance of life; Cryopreservation; Cryopreserved Tissue; Development; Devices; Disease; Dry Ice; Embryonic Development; Endocrine; Engineering; Equilibrium; Equipment; Evaluation; Failure; Family suidae; Feasibility Studies; Fertility; Fishes; Food; Formulation; Foundations; Freedom; Freezing; Germ Cells; Gold; Growth; Hematological Disease; High temperature of physical object; Hormones; Human; Ice; Immune; Individual; Infertility; Lead; Letters; Malignant Childhood Neoplasm; Malignant Neoplasms; Medicine; Metabolic Diseases; Methods; Modeling; Mus; National Institute of Child Health and Human Development; Oocytes; Organ; Organ Donor; Organ Preservation; Ovarian; Ovarian Tissue; Ovary; Patients; Perfusion; Periodicity; Phase; Preservation Technique; Primates; Production; Progress Reports; Protective Agents; Protocols documentation; Public Health; Rattus; Recovery; Reproductive Health; Reproductive Medicine; Reproductive Physiology; Research; Research Priority; Science; Sickle Cell; Sickle Cell Anemia; Small Business Innovation Research Grant; Societies; Stretching; Surgical Replantation; Survival Rate; Suspensions; System; Technology; Temperature; Testicular Tissue; Testis; Thermodynamics; Tissue Engineering; Tissue Preservation; Tissues; Translating; Transplantation; United States National Institutes of Health; Validation; Vascular Graft; Xenograft procedure; base; biomaterial compatibility; boys; cancer therapy; clinical application; clinical practice; clinically relevant; combinatorial; commercialization; cryogenics; design; experience; fertility preservation; girls; improved; in vivo; innovation; minimally invasive; next generation; nonhuman primate; novel; novel strategies; offspring; oncofertility; pediatric patients; phase 2 study; preconditioning; prepuberty; preservation; pressure; prototype; reproductive organ; restoration; scale up; service member; sperm cell; success; survivorship; tool; trauma care; young adult; young woman

ABSTRACT This project combines and further develops our ice-free isochoric vitrification platform, multi-step/multi-thermic machine perfusion, and next generation non-toxic cryopreservation cocktails to find a viable solution to the large public health need for fertility preservation in children and young adults after different diseases and disease treatments. Such technologies are urgently needed by 650,000 children and young adult cancer survivors in US, to help preserve fertility and restore endocrine function post toxic treatments. The NIH has recognized this as a top priority, the fourth of NICHDs Fertility and Infertility Branch’s SBIR priority research areas being focused on “Novel techniques for preservation of gametes and whole ovary and testes.” Using carefully optimized protocols and cryostasis cocktails, our team and others have successfully cryopreserved multiple tissues in an ice-free vitreous “glassy” or “amorphous” state, allowing for indefinite storage. Unfortunately, these advances in ice-free preservation have mostly not been successfully scaled beyond small-tissue and small-volume cell suspensions due to the high cryoprotectant chemical concentrations, and rapid cooling/warming rates necessary for current vitrification methods. However, our broader group together with Dr. Rubinsky at UC-Berkeley, have developed a scalable and biocompatible isochoric (constant volume) cryopreservation paradigm for completely ice-free vitrification. Building on the success of the Phase I feasibility study, this project will deliver: (i) an improved preservation and banking of ovarian tissues strips via ice-free equilibrium isochoric vitrification (compared to current gold-standard slow- freezing), (ii) comprehensive protocol for banking whole human ovaries with functional validation in human to mouse xeno-transplants and validation in non-human primates with embryo development and eventually healthy offspring, and (iii) clinically relevant prototype systems of isochoric vitrification, capable of banking whole ovaries (testes, or other similar size tissues) for years until re-plantation. In addition, this project provides tools, equipment, solutions and protocols with highly-translatable technology toward banking of whole vital organs, and other vascular grafts, addressing widespread needs for breakthroughs in biopreservation – from improved biospecimen preservation to vital organ banking and transplantation. To meet these objectives, in four specific aims, we (i) with the help of thermodynamic profiling, further optimize the composition of cryostasis solutions for isochoric vitrification with minimal pressures, (ii) refine the biocompatibility of the cocktails and protocols using ovarian tissue strips, with human-to-mouse xenotransplants and human blood vessels contractile functional assessment, (iii) scale to whole human ovary vitrification with multi-thermic machine perfusion and clinical grade isochoric devices, and as a capstone, (iv) cryobank whole non-human primate ovaries with ovarian tissue strips in vivo quality evaluation through minimally invasive autotransplantation, embryo development and eventual healthy offspring. Success of these novel approaches, individually or in combination, can enable further breakthroughs in oncofertility, biopreservation research, and clinical practice.

抽象的 该项目结合并进一步开发了我们的无冰等玻璃化平台，多步/多热机器 灌注和下一代无毒冷冻保存鸡尾酒可为大型公共卫生找到可行的解决方案 在不同的疾病和疾病治疗后，需要保存儿童和年轻人的生育能力。这样的 在美国，迫切需要650,000名儿童和年轻的成人癌症生存，以帮助维护生育能力 并恢复内分泌功能后有毒疗法。 NIH认为这是当务之急，是NICHD的第四个 生育能力和不育分支的SBIR优先研究领域侧重于“保存新技术 游戏，整个卵巢和睾丸。” 使用精心优化的方案和低温鸡尾酒，我们的团队和其他人成功保存了冷冻保存 无冰的玻璃体“玻璃”或“无定形”状态中的多个时间安排，允许无限期存储。不幸的是，这些 无冰制剂的进步大多未成功地缩放到小组织和小体积细胞之外 由于高冷冻保护剂化学浓度而引起的悬浮液，以及必要的快速冷却/变暖速率 当前的玻璃化方法。但是，我们与UC-Berkeley的Rubinsky博士一起开发了更广泛的小组 可伸缩且具有生物相容性的异位（恒定体积）冷冻保存范式，用于完全无冰的玻璃化。 基于I阶段可行性研究的成功，该项目将提供：（i）改进的保存和 通过无冰平衡等速玻璃化卵巢组织条带（与当前的金标准慢相比 冻结），（ii）用于在人类到鼠标功能验证的整个人类卵巢的综合协议 异种移植物和非人类隐私的验证，并具有胚胎开发，最终健康的后代， （iii）等效玻璃化的临床相关原型系统，能够储存整个卵巢（睾丸或其他 类似的组织）多年来，直到重新植入。此外，该项目还提供工具，设备，解决方案和 具有高度转化技术的协议，用于整个重要器官和其他血管移植的协议，以解决 在生物保存中突破的宽度需求 - 从改进的生物环境保存到重要器官 银行和移植。 为了实现这些目标，在四个特定目标中，我们（i）在热力学分析的帮助下，进一步优化了 低温溶液对等速玻璃化的组成，并具有最小的压力，（ii）提高了生物相容性 使用卵巢组织带，人向小鼠的异种移植和人类血管的鸡尾酒和方案 收缩功能评估，（iii）用多热机灌注和 临床等级等级设备，作为顶峰，（iv）Cryobank整个非人类灵长类动物卵巢具有卵巢组织 通过微创自动解剖，胚胎开发和最终的微创自身移植，最终的体内质量评估。 健康的后代。这些新颖的方法是单独或结合的，可以实现进一步的突破 在良好，生物保存研究和临床实践中。