Cryopreservation and Transplantation of Ovarian Cortical Tissue for Fertility Preservation

卵巢皮质组织的冷冻保存和移植以保存生育能力

• 批准号: 9920744
• 负责人: Mary B Zelinski
• 金额: $ 58.81万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-06 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920744
• 关键词: 3-Dimensional; Adolescent; Adolescent and Young Adult; Adult; Age; Antral; Autologous; Autologous Transplantation; Benign; Biomedical Engineering; Birth; Blood Vessels; Blood flow; Bone Marrow Transplantation; Breast Cancer Patient; Cancer Survivor; Chemotherapy and/or radiation; Child; Clinic; Clinical; Complex; Computer Models; Controlled Study; Cortex of ovary; Cryopreservation; Detection; Development; Diagnosis; Disease; Embryo; Embryology; Embryonic Development; Encapsulated; Endocrine; Environment; Exposure to; FDA approved; Female; Fertility; Fibrin; Foundations; Freezing; Future; Germ Cells; Goals; Health; Heterotopic Transplantation; Human; In Vitro; Individual; Infertility; Interruption; Investigation; Investigational Therapies; Late Effects; Macaca mulatta; Malignant Neoplasms; Menopause; Methods; Modeling; Mothers; Non-Malignant; Oocytes; Ovarian; Ovarian Tissue; Ovarian tissue cryopreservation; Ovary; Parents; Patients; Population; Premature Menopause; Premature Ovarian Failure; Prior Therapy; Production; Protocols documentation; Radiation therapy; Regulation; Reporting; Reproducibility; Research Personnel; Risk; Running; Safety; Site; Source; Stromal Cells; Survival Rate; Survivors; System; Techniques; Technology; Tissue Transplantation; Tissues; Translations; Transplantation; Ultrasonography; Woman; cancer cell; cancer invasiveness; cancer therapy; cell type; child bearing; childhood cancer survivor; clinical practice; clinical translation; contrast enhanced; cryobiology; embryo cryopreservation; experience; fertility preservation; functional outcomes; girls; improved; in vivo; innovative technologies; nonhuman primate; novel; novel strategies; offspring; oocyte cryopreservation; oocyte quality; ovarian failure; ovary transplantation; post-transplant; pre-clinical research; preimplantation; prepuberty; preservation; public health relevance; restoration; scaffold; side effect; sound; steroid hormone; tool; treatment effect; vascular bed; young adult; young woman

 DESCRIPTION (provided by applicant): The long-range goals of this proposal are to develop robust and reproducible methods for ovarian tissue cryopreservation and transplantation as options for fertility preservation in survivors of cancer or other benign conditions wherein ovaria function is compromised. While 80% of young patients currently survive their cancers, devastating side effects of chemo- or radiotherapies leave female survivors facing infertility due to ovarian failure. Cryopreservation of ovarian tissue remains the only option for prepubertal, adolescent and young women with cancer as well as adult patients for whom immediate cancer therapy is required. But, human ovarian tissue cryopreservation is considered experimental and hampered by several factors. Embryology clinics in the U.S. favor embryo and oocyte vitrification over slow-rate freezing, but there is no uniform protocol for vitrification of ovaria tissue. Although 30 human births have been reported from slow-rate freezing and transplantation to orthotopic sites, only 4 could claim that the transplanted tissue was known to be the source of the oocytes. Most young survivors will not have a healthy ovarian vascular bed as a transplantation site following cancer therapies. Cryopreservation is also the only option for patients contraindicated for ovarian transplantation due to the risk of reintroducing malignant cells. While in vitro follicle culture is under development, most studies use follicles isolated frm non-cryopreserved tissues. We successfully devised a method for vitrification of rhesus monkey ovarian tissue in a closed system, and demonstrated post-thaw function in vivo and in vitro. When transplanted to heterotopic sites, vitrified tissue resumes ovarian function, and yields mature oocytes capable of preimplantation embryonic development. Secondary follicles isolated from vitrified tissue and encapsulated for 3-dimensional (3D) culture survive, grow to antral stages and produce steroid hormones in vitro, but oocyte quality is poor. Since the ovarian cortex is composed of complex cell types that complicate cryopreservation, vitrification of individual follicles and subsequent 3D culture is a novel approach toward preserving gametes for young patients with highly invasive cancers. An elite panel of co-investigators and collaborators that bring expertise in both state-of-the-art cryobiology as well as pre-eminent experience in clinical ovarian transplantation will help us advance the current technology for more rapid translation to clinical practice for patients. Using the rhesus monkey, we propose to identify the transplantation site for optimal fertile function of both prepubertal and young adult ovarian cortical tissue, improve long-term transplant function via local administration of factors important for revascularization as well as follicular survival, and optimize vitrification of isolaed preantral follicles and their ability to yield competent oocytes following 3D culture in vitro. Liv births in nonhuman primates after these controlled studies will establish the safety and feasibilit of experimental therapies prior to clinical translation so girls and young women can be offered the best chances of becoming mothers after surviving cancer.



项目成果

Comparison of dilute and nondilute osmotic equilibrium models for erythrocytes.

• DOI: 10.1016/j.cryobiol.2022.09.001
• 发表时间: 2022-09
• 期刊: Cryobiology
• 影响因子: 2.7
• 作者: R. Shuttleworth;A. Higgins;A. Eroglu;J. Benson

Vitrification preserves murine ovarian follicular cell transcriptome in a 3D encapsulated in vitro follicle growth system.

玻璃化冷冻在 3D 封装的体外卵泡生长系统中保存小鼠卵巢卵泡细胞转录组。

• DOI: 10.1093/biolre/ioab185
• 发表时间: 2021
• 期刊: Biology of reproduction
• 影响因子: 3.6
• 作者: Wang,Yingzheng;Drake,RileyS;Russo,DanielaD;Pattarawat,Pawat;Zhang,Qiang;Zelinski,MaryB;Shalek,AlexK;Goods,BrittanyA;Xiao,Shuo
• 通讯作者: Xiao,Shuo