Microencapsulation of oocytes for low-CPA (cryoprotectant) vitrification

用于低 CPA（冷冻保护剂）玻璃化冷冻的卵母细胞微囊化

基本信息

批准号：
8600270
负责人：
Xiaoming He
金额：
$ 33万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8600270
关键词：
Affect Alginates Benchmarking Biological Models Biological Preservation Breeding Caliber Cell Survival Cells Cryopreservation Dehydration Development Devices Effectiveness Electrostatics Embryo Encapsulated Equilibrium Exposure to Fertility Fertilization in Vitro Freezing Future Goals Human Ice In Vitro Injury Kinetics Life Liquid substance Livestock Maintenance Mammalian Cell Mammals Mechanics Medical Metabolic Methods Microcapsules drug delivery system Microencapsulations Modeling Oocytes Outcome Performance Peromyscus Phase Transition Procedures Protocols documentation Public Health Quartz Radiosurgery Reproductive Medicine Research Solutions Stress Techniques Testing Time Water Woman Work animal resource cell injury chemotherapy gonad function improved in vivo nanolitre new technology novel novel strategies occupational hazard public health relevance

项目摘要

DESCRIPTION (provided by applicant): Oocyte cryopreservation is of great importance to the advancement of assisted reproductive medicine, maintenance of animal resources, and livestock management. However, the commonly used methods today for oocyte cryopreservation by either slow-freezing or conventional vitrification have inherent drawbacks. For example, the slow-freezing (freezing: the transition of liquid water into ice crystal) approach is associated with inevitable cell injury due to ice formation and slow- freezing induced cell dehydration. The unusually high CPA (cryoprotectant) concentration (4 - 7 M) required by the conventional vitrification (vitrification: the transition of liquid water into an amorphous, glassy state rather than ice crystal) method can result in significant metabolic and osmotic injury in living cells even in a short exposure time of only a few minutes. Presumably, it is these inherent drawbacks that are responsible for the dismal outcome of oocyte cryopreservation to date. The goal of the proposed research outlined in this R01 proposal is to develop new strategies for cell cryopreservation by microencapsulating the cells in alginate microcapsule to vitrify at a low-CPA (low and non- toxic amount of cryoprotectants, = 1.5 M) concentration. The proposed low-CPA vitrification approach combines all the advantages of the commonly used slow-freezing and conventional vitrification techniques today while avoiding all their shortcomings. Oocytes of the naturally bred (outbred) Peromyscus will be used as the biological model in this project so that the results obtained from the proposed studies can be more transferable to achieve low-CPA vitrification of oocytes of other naturally bred mammals including humans. In addition, Peromyscus embryos will be used as the benchmark biological model in this project to test the new approach in view of the fact that embryo cryopreservation has been successful in general. It is believed that the proposed research and the novel low-CPA vitrification approach will have a significant impact on the field of oocyte cryopreservation for assisted reproductive medicine, maintenance of animal resources, and livestock management. PUBLIC HEALTH RELEVANCE: Oocyte cryopreservation is of great importance to the advancement of assisted reproductive medicine. We propose to develop a novel technology to achieve much improved performance for oocyte cryopreservation. This research will have a significant impact on the preservation of future fertility of women who may lose gonadal function because of exposure to environmental/occupational hazards or aggressive medical treatments such as extirpative surgery, radiation, and chemotherapy.

描述（由申请人提供）：卵母细胞冷冻保存对于辅助生殖医学，动物资源的维护和牲畜管理非常重要。但是，当今通过缓慢冻结或常规玻璃化来进行卵母细胞冷冻保存的方法具有固有的缺点。例如，缓慢冻结（冷冻：液体水向冰晶体的过渡）方法与由于冰的形成和缓慢的冷冻诱导的细胞脱水而导致的细胞损伤有关。常规玻璃化（玻璃化：将液体水转换为无定形的，玻璃状的而非冰晶体）所需的异常高的CPA（冷冻保护剂）浓度（4-7 m）可能会导致活细胞中显着的代谢和渗透损伤。据推测，正是这些固有的缺点是迄今为止卵母细胞冷冻保存的惨淡结果。 R01提案中概述的拟议研究的目的是通过将藻酸盐微胶囊中的细胞微封闭细胞以在低CPA（低CPA（低毒性和非毒性的冷冻保护剂）液体下，开发新的策略来制定细胞冷冻保存，= 1.5 m）。提出的低CPA玻璃化方法结合了当今常用的慢冻和常规玻璃化技术的所有优点，同时避免了所有缺点。天然繁殖（杂种）peromyscus的卵母细胞将用作该项目的生物学模型，以便从提出的研究中获得的结果可以更可转移，以实现其他天然繁殖哺乳动物的卵母细胞的低CPA玻璃化。此外，鉴于胚胎冷冻保存一般而言，Peromyscus胚胎将用作该项目的基准生物学模型，以测试新方法。据信，拟议的研究和新型的低CPA玻璃化方法将对卵母细胞冷冻保存领域产生重大影响，用于辅助生殖医学，维持动物资源和牲畜管理。公共卫生相关性：卵母细胞冷冻保存对于辅助生殖医学的发展至关重要。我们建议开发一种新颖的技术，以实现卵母细胞冷冻保存的大大提高。这项研究将对可能失去性腺功能的未来生育能力产生重大影响，这些妇女因受到环境/职业危害或积极的医疗治疗，例如消除手术，放射和化学疗法而失去性腺功能。