Towards Mammalian Limb Regeneration

迈向哺乳动物肢体再生

• 批准号: 7994509
• 负责人: CRAIG M CREWS
• 金额: $ 31.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7994509
• 关键词: Amputation; Amputees; Biological Models; Candidate Disease Gene; Developmental Biology; Digit structure; Doctor of Philosophy; Embryo; Epidermis; Foundations; Future; Genes; Goals; Human; Knowledge; Limb structure; Mammals; MicroRNAs; Molecular; Mus; Natural regeneration; Orthologous Gene; Regenerative Medicine; Salamander; System; Universities; Work; Wound Healing; base; clinical application; comparative; gene therapy; limb regeneration; public health relevance; regenerative; response; small molecule; wound

DESCRIPTION (provided by applicant): Advances in regenerative medicine offer great potential for the treatment of limb amputees. However, despite an increasing understanding of the molecular mechanisms underlying regenerative responses in model systems (e.g., salamander limb regeneration), the application of this knowledge to mammalian systems is lagging. With the ultimate goal of inducing mammalian limb regeneration, we propose here to apply the results gained from recent studies on the wound epidermis formed during salamander limb regeneration to a non-regenerative system, i.e., mouse digit amputation wounds. Specifically, we hypothesize that the murine orthologs of those genes and microRNAs identified in regenerating salamander limbs can initiate mammalian regeneration when ectopically expressed. If successful, the basic knowledge gained from these unprecedented studies will have a significant impact on tissue repair, wound healing and comparative developmental biology. Moreover, this work will provide the foundation for future human limb regeneration clinical applications. PUBLIC HEALTH RELEVANCE: Advances in regenerative medicine offer great potential for the treatment of limb amputees. However, despite an increasing understanding of the molecular mechanisms underlying regenerative responses in model systems (e.g., salamander limb regeneration), the application of this knowledge to mammalian systems is lagging. With the ultimate goal of inducing mammalian limb regeneration, we propose here to apply the results gained from recent studies on the wound epidermis formed during salamander limb regeneration to a non-regenerative system, i.e., mouse digit amputation wounds.

描述（由申请人提供）：再生医学的进步为截肢者的治疗提供了巨大的潜力。然而，尽管对模型系统中再生反应的分子机制的理解越来越多（例如，蝾螈肢体再生），这方面的知识应用到哺乳动物系统是滞后的。以诱导哺乳动物肢体再生为最终目标，我们建议将最近对蝾螈肢体再生过程中形成的伤口表皮的研究结果应用于非再生系统，即，老鼠手指截肢的伤口具体来说，我们假设，这些基因和microRNA再生蝾螈肢体中确定的小鼠直系同源物可以启动哺乳动物再生时异位表达。如果成功，从这些前所未有的研究中获得的基础知识将对组织修复，伤口愈合和比较发育生物学产生重大影响。此外，这项工作将为未来人类肢体再生的临床应用奠定基础。 公共卫生相关性：再生医学的进步为截肢者的治疗提供了巨大的潜力。然而，尽管对模型系统中再生反应的分子机制的理解越来越多（例如，蝾螈肢体再生），这方面的知识应用到哺乳动物系统是滞后的。以诱导哺乳动物肢体再生为最终目标，我们建议将最近对蝾螈肢体再生过程中形成的伤口表皮的研究结果应用于非再生系统，即，老鼠手指截肢的伤口