RO1A: Novel Methods for Cryopreservation and Recovery of Human Follicles (2/10)

RO1A：人类卵泡冷冻保存和恢复的新方法 (2/10)

基本信息

批准号：
8105450
负责人：
Mary B Zelinski
金额：
$ 39.68万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8105450
关键词：
Adult Age Biological Preservation Cancer Survivor Cells Characteristics Child Clinical Medicine Controlled Clinical Trials Crying Cryopreservation Cryoprotective Agents Development Diagnosis Discipline Endocrinologist Ethics Failure Female Fertility Fertilization Future Goals Human Ice In Vitro Incidence Individual Infertility Knowledge Live Birth Macaca mulatta Malignant Childhood Neoplasm Malignant Neoplasms Measures Methods Modeling Newly Diagnosed Oocytes Osmolalities Ovarian Ovarian Tissue Ovary Patients Permeability Population Pregnancy Premature Ovarian Failure Primates Procedures Radiation therapy Recovery Relative (related person)Reporting Reproductive Physiology Research Risk Science Scientist Series Social Sciences Stress Survival Rate Teenagers Temperature Testing Tissues Training Translating Transplantation Woman Work base cancer diagnosis cancer therapy chemotherapy cryobiology design human subject improved male mathematical model nonhuman primate novel programs reproductive research study sound sperm cell success

项目摘要

In 2006 alone, nearly 55,000 women either prior to or in their reproductive age range are expected to be diagnosed with cancer. For females undergoing radio- or chemotherapy for cancer treatment, iatrogenic damage to the ovaries is common, often resulting in infertility. Significant advances in treatment during the past few decades have improved the survival significantly among individuals diagnosed with cancer; the 5- year relative survival rate for all cancers diagnosed between 1995 and 2001 is 65%. It has been estimated that; by 2010, 1 in 250 people in the adult population will be cancer survivors. The remarkable success of improved cancer therapy has generated a significant societal need: namely, the development of effective means to preserve the fertility of individuals undergoing such therapies. Currently, all forms of female fertility preservation are considered experimental. Cryopreservation of cells and tissues is an interplay of as many as 8-12 factors, most of which interact. By establishing a clear understanding of the underlying fundamental cryobiological characteristics of the cells or tissues, we can develop mathematical models that enable us to design optimal methods. The overall goal of R01A under the auspices of the Oncofertility Consortium is to develop improved methods to cryopreserve primate oocvtes. immature follicles and ovarian tissue, based upon sound, fundamental crvobiological principles. We propose the following specific aims for this project: (1) develop and empirically test an optimized method for cryopreserving rhesus and human in vitro matured oocytes; (2): develop and empirically test an optimized method for cryopreserving rhesus and human immature follicles; (3): develop and empirically test an optimized method for cryopreserving rhesus and human ovarian cortical tissue. We are proposing a series of experiments to determine the tolerance of cells crucial for female fertility to several stresses associated with Cryopreservation including changes in temperature, osmolality, and cryoprotective agents. In addition, we are proposing experiments designed to understand biophysical characteristics of oocytes, follicles, and ovarian tissue, such as the permeability of the cells to cryoprotectants and the intracellular ice formation characteristics of whole ovarian tissue pieces. Used in conjunction with the tolerances of the cells to the stresses as described above, the resulting information will allow the development of theoretically-optimal Cryopreservation procedures. We will test these procedures using in vitro maturation, fertilization, and development as experimental endpoints. We will initially conduct all of the experiments using rhesus macaque oocytes, follicles and ovarian tissue. As new knowledge is gained from this approach and improved methods for Cryopreservation are developed, we will apply these developments to human oocytes, follicles and ovarian tissue working with the R01B in nonhuman primates, R01C human follicles and in conjuction with each of the training and social science programs (R01D, R25, T90/R90, K01).

仅在2006年，就在2006年，预计将有近55,000名妇女在生殖年龄范围内被诊断出患有癌症。对于接受癌症治疗的放射性或化学疗法的女性，医源性对卵巢的损害很常见，通常导致不育。在治疗过程中的重大进展过去几十年来，在被诊断出患有癌症的个体中的生存显着提高。 5- 在1995年至2001年期间诊断出的所有癌症的年度相对存活率均为65％。据估计那;到2010年，成年人口中有250人将是癌症幸存者。杰出的成功改善的癌症疗法产生了巨大的社会需求：即有效的发展意味着保持接受此类疗法的人的生育能力。目前，所有形式的女性生育能力保存被认为是实验性的。细胞和组织的冷冻保存是尽可能多的相互作用作为8-12个因素，其中大多数相互作用。通过对基本基本的清晰了解细胞或组织的冷冻生物学特征，我们可以开发数学模型，使我们能够设计最佳方法。 R01A的总体目标是在Oncofertility联盟的主持下开发了改进的方法来冷冻保存灵长类动物。未成熟的卵泡和卵巢组织，基于根据声音，基本的CRVOBIological原则。我们提出以下针对该项目的具体目标：（1）开发和经验测试一种优化的冷冻恒晶和人类体外成熟的方法卵母细胞；（2）：开发和经验测试一种优化的冷冻恒星和人类的方法未成熟的卵泡；（3）：开发和经验测试一种优化的冷冻恒星和人卵巢皮质组织。我们正在提出一系列实验来确定细胞的耐受性对于与冷冻保存相关的几种压力，包括女性生育至关重要温度，渗透压和冷冻保护剂。此外，我们提出了设计用于的实验了解卵母细胞，卵泡和卵巢组织的生物物理特征，例如渗透性将整个卵巢组织碎片的冷冻保护剂和细胞内冰的形成特征。如上所述，与细胞对应力的耐受性结合使用信息将允许制定理论上的冷冻保存程序。我们将测试这些程序使用体外成熟，受精和发育作为实验终点。我们将最初使用恒河猴，卵泡和卵巢组织进行所有实验。作为新从这种方法中获得知识，并开发了改进的冷冻保存方法，我们将将这些发展应用于非人类的R01b的人类卵母细胞，卵泡和卵巢组织灵长类动物，R01C人卵泡，并与每种培训和社会科学结合程序（R01D，R25，T90/R90，K01）。