ICE-FREE PRESERVATION OF OVARIES FOR LONG-TERM FECUNDITY

无冰保存卵巢以实现长期生育能力

基本信息

批准号：
6790139
负责人：
Ying Song
金额：
$ 11.91万
依托单位：
ORGAN RECOVERY SYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-23 至 2006-03-22
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6790139
关键词：
SCID mouse cell morphology cryopreservation cryoscience cytoprotection fertility glass ovary physical state sheep statistics /biometry technology /technique development tissue /organ preservation tissue resource /registry

项目摘要

DESCRIPTION (provided by applicant): There are more than 50,000 reproductive age women who are exposed to sterilizing chemotherapy and radiotherapy annually in the U.S. alone and thousands lose their ovarian function due to gynecologic surgery. Cryopreservation of ovarian tissue prior to initiation of cancer therapy, followed by autologous transplantation or in vitro maturation and in vitro fertilization after remission, could provide a means of protecting and replacing gonadal function and fertility. The destructive effects of extracellular ice formation caused by conventional cryopreservation by freezing are the major obstacle for cryopreservation of ovarian tissues. It is now well established that long-term storage of complex multicellular tissues, the integrity of which is compromised by ice formation, will best be achieved using techniques that minimize, or avoid the formation of ice. We have successfully developed vitrification method in blood vessel and articular cartilage models. The goal of this study is to investigate the effects of vitrification on structural and functional viability of ovaries compared with a conventional freezing cryopreservation method. The criteria for determining feasibility of vitrification for preserving ovaries will be (1) the demonstration of freedom from extracellular and intracellular ice formation in vitrified specimens, and (2) statistically significant differences in cell viability and follicle survival rates between ice-free cryopreserved and conventionally frozen ovaries. To our knowledge, vitrification has not previously been used for storage of large segment ovaries. This study will advance the commercial application of cryobiology in reproductive medicine. This research project is the first step towards establishment of an ovary bank for the processing, storage and distribution of the cryopreserved ovarian tissue for clinical use. Following successful completion of the aim of this Phase I SBIR proposal, several issues must be addressed in a subsequent Phase II SBIR submission. These include (1) optimization of the vitrification solutions and protocols for banking of ovaries including the development of effective methods for transportation of vitrified ovaries, (2) further investigation of the effects of cryopreservation variables upon follicle growth after in vitro maturation, and (3) in vivo evaluation of cryopreserved ovaries in a large animal (sheep) model.

描述（由申请人提供）：仅在美国，每年就有超过 50,000 名育龄妇女接受绝育化疗和放疗，其中数千人因妇科手术而丧失卵巢功能。在开始癌症治疗之前冷冻保存卵巢组织，然后在缓解后进行自体移植或体外成熟和体外受精，可以提供保护和替代性腺功能和生育能力的方法。传统冷冻冷冻技术所造成的细胞外冰形成的破坏作用是卵巢组织冷冻保存的主要障碍。现在已经确定的是，复杂多细胞组织的完整性因冰的形成而受到损害，最好使用最大限度地减少或避免冰的形成的技术来实现。我们成功开发了血管和关节软骨模型的玻璃化冷冻方法。本研究的目的是研究与传统冷冻保存方法相比，玻璃化冷冻对卵巢结构和功能活力的影响。确定玻璃化冷冻保存卵巢可行性的标准是（1）证明玻璃化标本中没有细胞外和细胞内冰形成，以及（2）无冰冷冻保存与传统冷冻保存的细胞活力和卵泡存活率之间存在统计学上的显着差异冷冻卵巢。据我们所知，玻璃化冷冻以前尚未用于储存大段卵巢。这项研究将推动冷冻生物学在生殖医学中的商业应用。该研究项目是建立卵巢库的第一步，用于处理、储存和分配临床使用的冷冻卵巢组织。在成功完成第一阶段 SBIR 提案的目标后，必须在随后的第二阶段 SBIR 提交中解决几个问题。这些包括（1）优化玻璃化冷冻解决方案和卵巢储存方案，包括开发玻璃化卵巢运输的有效方法，（2）进一步研究冷冻保存变量对体外成熟后卵泡生长的影响，以及（3 ）大型动物（绵羊）模型中冷冻卵巢的体内评估。