The Study and Transplantation of Male Germ Cells

雄性生殖细胞的研究与移植

• 批准号: 312091-2012
• 负责人: Honaramooz, Ali
• 金额: $ 1.97万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630965
• 关键词: Study; Transplantation; Male; Germ; Cells

Spermatogonial stem cells (SSCs) are the only adult stem cells that can contribute genes to the next generation by producing unlimited numbers of sperm. However, our knowledge of SSCs is limited because important questions regarding their unique identity and mechanisms critical for maintaining their "stem-ness" remain unanswered. We have established a system for "germ cell transplantation (GCT) in farm animals", in which SSCs are obtained from a donor pig, genes of interest are inserted, then the SSCs are transferred into the testes of unrelated (and immune-competent) pigs. Breeding of such a recipient animal can pass the genetic modifications on to progeny. Therefore, GCT is a novel approach for the production of genetically-modified (transgenic) farm animals that can potentially produce important therapeutic proteins in their milk (i.e., dairy animals), serve as valuable animal models for biomedical research, or in the future produce "humanized" tissues/organs (i.e., pigs) for xenotransplantation into patients. GCT has the potential to be a more efficient, less time consuming, and less costly method for generating transgenic farm animals than current technologies (e.g., cloning). GCT can also preserve genetic material of prized animals, can be used as a bioassay to assess the cause of infertility, and could have clinical applications in restoring fertility lost due to treatment in cancer patients. NSERC Discovery funding will enable the continuation of my research program on the biology and application of SSCs by: 1) identifying genes uniquely expressed by SSCs that can aid in their study and selection; 2) optimizing cell culture conditions for SSCs to promote their propagation for subsequent GCT; and 3) preparing recipient testes to facilitate the implantation of donor cells. This research will train 2 PhD students and 5 summer undergraduate students, who upon completion will be well positioned to pursue further studies or careers in veterinary medicine or reproductive biology.

精原干细胞（SSCs）是唯一可以通过产生无限数量的精子为下一代贡献基因的成体干细胞。然而，我们的知识是有限的，因为重要的问题，他们的独特身份和机制的关键，以保持他们的“干”仍然没有答案。我们已经建立了一个“农场动物生殖细胞移植（GCT）”系统，其中从供体猪获得精原干细胞，插入感兴趣的基因，然后将精原干细胞转移到无关（和免疫活性）的猪的睾丸中。这种受体动物的育种可以将遗传修饰传递给后代。因此，GCT是一种用于生产遗传修饰（转基因）农场动物的新方法，所述农场动物可以潜在地在其乳中产生重要的治疗性蛋白质（即，产奶动物），用作生物医学研究的有价值的动物模型，或者在将来产生“人源化”组织/器官（即，猪）用于异种移植到患者体内。GCT具有成为比当前技术（例如，克隆）。GCT还可以保存珍贵动物的遗传物质，可用作评估不孕症原因的生物测定，并可用于恢复癌症患者因治疗而丧失的生育能力。NSERC发现资金将使我的研究计划的生物学和应用的SSC的继续：1）确定基因的独特表达的SSC，可以帮助他们的研究和选择; 2）优化细胞培养条件的SSC，以促进其繁殖为随后的GCT;和3）准备受体睾丸，以促进供体细胞的植入。这项研究将培养2名博士生和5名暑期本科生，他们完成后将有能力在兽医或生殖生物学领域继续深造或从事职业。