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Mechanoregulation of Tissue Morphogenesis

组织形态发生的机械调节

基本信息

批准号：
7981040
负责人：
Pak Kin Wong
金额：
$ 227.25万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2015-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (Provided by the applicant) Abstract: Mechanoregulation of Tissue Morphogenesis Abstract Regenerative medicine holds great promise in treating degenerative diseases by stimulating damaged tissues to repair themselves, or replacing them with engineered tissues when the body cannot heal itself. A fundamental understanding of the regulatory mechanisms in tissue regeneration and the ability to modulate these processes, therefore, are critical to the ultimate success of regenerative medicine. Deviations of the regulatory processes as a result of genetic variation or environmental factors also represent the underlying causes of many diseases. However, little is known about how multi-progenitor systems interpret the cues in the microenvironment, such as global geometric guidance, local cell-cell interactions, and extracellular matrix properties, to collectively drive the morphogenic process of fashioning tissue structures across multiple length scales. Our recent studies suggest novel mechanoregulation schemes utilized by myogenic progenitors in the organization of striated muscle. The objective of this application is to develop an innovative cell mechanoregulation approach equipped with a set of novel technological modularities to elucidate the complex regulatory mechanisms during cellular self-organization. As a model system, the multi-stage myogenic self-organization process involving polarization, alignment, fusion, and myofibrillogenesis of muscle progenitors will be used to decipher the mechanoregulation of cellular self-organization during myogenesis. The project will address the long-standing biological question of multi-cellular self- organization, which drives the emergence of tissue morphogenesis. Successful completion of the project will establish the mechanoregulation approach for elucidating the regeneration processes of various tissues and will have profound impact on regenerative medicine in the future. Public Health Relevance: Regenerative medicine holds great promise in treating degenerative diseases by stimulating damaged tissues to repair themselves, or replacing them with engineered tissues when the body cannot heal itself. The proposed cell mechanoregulation study will allow us to understand the basic processes that govern the formation of tissue during normal development and diseases, and will eventually lead to novel approaches in regenerative medicine.

描述（由申请人提供）摘要：组织形态发生的机械调节摘要再生医学通过刺激受损组织进行自我修复，或在身体无法自我修复时用工程组织替代它们，在治疗退行性疾病方面具有广阔的前景。因此，对组织再生调节机制的基本了解以及调节这些过程的能力对于再生医学的最终成功至关重要。由于遗传变异或环境因素而导致的调节过程的偏差也是许多疾病的根本原因。然而，人们对多祖细胞系统如何解释微环境中的线索（例如全局几何引导、局部细胞间相互作用和细胞外基质特性）以共同驱动跨多个长度尺度的组织结构的形态发生过程知之甚少。我们最近的研究表明，肌原祖细胞在横纹肌组织中利用了新颖的机械调节方案。该应用的目的是开发一种创新的细胞机械调节方法，配备一套新颖的技术模块，以阐明细胞自组织过程中的复杂调节机制。作为模型系统，涉及肌肉祖细胞的极化、排列、融合和肌原纤维发生的多阶段肌源自组织过程将用于破译肌发生过程中细胞自组织的机械调节。该项目将解决多细胞自组织这一长期存在的生物学问题，该问题推动了组织形态发生的出现。该项目的成功完成将建立阐明各种组织再生过程的机械调节方法，将对未来的再生医学产生深远影响。公共健康相关性：再生医学通过刺激受损组织进行自我修复，或在身体无法自我修复时用工程组织替代它们，在治疗退行性疾病方面具有广阔的前景。拟议的细胞机械调节研究将使我们能够了解正常发育和疾病期间控制组织形成的基本过程，并最终导致再生医学的新方法。