Repair and regeneration in a novel animal model

新型动物模型的修复和再生

• 批准号: 7340385
• 负责人: Cheng-Ming Chuong
• 金额: $ 6.55万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7340385
• 关键词: Adult; Amphibia; Amputation; Animal Model; Animals; Apoptosis; Appendix; Back; Biology; Birds; Caenorhabditis elegans; Cell Proliferation; Cells; Chromatin; Development; Digit structure; Drosophila genus; Electroporation; Engineering; Event; Fibroblast Growth Factor; Figs - dietary; Fishes; Fracture; Goals; Grant; Hair; Human; Injury; Knowledge; Label; Learning; Limb structure; Lizards; Malignant Neoplasms; Mammals; Maps; Medicine; Mind; Molecular; Molting; Morphogenesis; Natural regeneration; Nature; Organ; Paper; Pathway interactions; Physiological; Physiological Processes; Preparation; Process; Property; Publications; Publishing; Regenerative Medicine; Reptiles; Research; Signaling Molecule; Small Interfering RNA; Stem Cell Research; Stem cells; Stress; Tail; Techniques; Testing; Thinking; Tissue Engineering; Tissues; Vertebrates; Work; Wound Healing; Xenopus; Zebrafish; appendage; beta catenin; blastema; clinical application; fascinate; forging; human study; improved; in vivo Model; migration; novel; organ regeneration; precursor cell; repaired; response; size

DESCRIPTION (provided by applicant): Regenerative medicine and tissue engineering have emerged as some of the most fascinating fields with potentially high clinical applications. If an adult human unfortunately loses a digit or limb, the wounds heal without signs of regeneration. Among amniotes, some lizards show a remarkable ability to regenerate tails following amputation. Here we propose to develop this unique in vivo model of regeneration to understand the unique molecular/ cellular mechanisms underlying repair and regeneration. The long term goal is to learn how animals do this process in Nature and to be able to apply these principles to benefit regeneration and bio-engineering following human amputation (e.g., limb, digit). Examples of ideal animal models that helped to improve our understanding of physiological and pathological phenomena include the use of Drosophila, C. elegans, etc. A unique phenomenon in reptiles is "autotomy" in which the stressed lizards automatically break their tails at specific fracture planes. Regeneration then initiates from these planes. Since this becomes part of the "physiological" process, we hypothesize that stem cells may reside in niches located near the facture plane, similar to bulge stem cells in hair molting cycles. Alternatively, cells in wounds may undergo de- differentiation to generate pluri-potential blastema. In either case, the regeneration is initiated and tissue morphogenesis progresses beyond simple repair. To test for these possibilities, we will pursue the following aims. 1) Characterize the regenerative events following wounding of reptile tails, including cell proliferation, apoptosis and migration. 2) Locate the origin of precursor cells in regenerating reptile tails, including the use of long-term label retention and chromatin status markers. 3) What molecular events are involved during reptile tail regeneration? Development related signaling molecule pathways (e.g., Msx, beta catenin, Shh, BMP, FGF, etc.) will be prioritized for mapping studies. Likely candidates will be perturbed using electroporation of siRNA.

描述（由申请人提供）：再生医学和组织工程已成为一些最迷人的领域，具有潜在的临床应用。如果不幸的是，成年人失去了数字或肢体，伤口愈合而没有再生迹象。在羊膜中，一些蜥蜴在截肢后显示出了出色的尾巴再生能力。在这里，我们建议开发这种独特的体内再生模型，以了解修复和再生的独特分子/细胞机制。长期目标是了解动物在本质上如何进行此过程，并能够应用这些原则以使人类截肢后的再生和生物工程受益（例如，肢体，数字）。有助于提高我们对生理和病理现象的理解的理想动物模型的例子包括使用果蝇，秀丽隐杆线虫等。爬行动物中的独特现象是“自动造口”，其中压力蜥蜴会自动在特定的骨折平面上折断尾巴。然后再生从这些平面发起。由于这成为“生理”过程的一部分，因此我们假设干细胞可能位于位于态面附近的壁ni中，类似于头发摩尔循环中的凸起的干细胞。另外，伤口中的细胞可能会进行分化以产生pluri电势囊肿。无论哪种情况，都会开始再生，组织形态发生的发展是无法简单修复的。为了测试这些可能性，我们将追求以下目标。 1）表征爬行动物尾巴受伤后的再生事件，包括细胞增殖，凋亡和迁移。 2）将前体细胞的起源定位在再生爬行动物尾部，包括使用长期标记保留和染色质状态标记。 3）在爬行动物尾部再生过程中涉及哪些分子事件？与开发相关的信号分子途径（例如MSX，β链球菌，SHH，BMP，FGF等）将优先用于映射研究。可能会使用siRNA的电穿孔来扰动候选人。