SKELETAL MUSCLE STEM CELLS FOR TISSUE REPAIR

用于组织修复的骨骼肌干细胞

• 批准号: 6779202
• 负责人: RANDALL H KRAMER
• 金额: $ 34.09万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6779202
• 关键词: bioengineering /biomedical engineering; biotechnology; bone regeneration; cell differentiation; cleft lip; cleft palate; clinical research; congenital oral /facial /cranial defect; gene expression; human tissue; integrins; laboratory mouse; muscle satellite cell; muscular dystrophy; myoblasts; myogenesis; protein structure function; regeneration; striated muscles; technology /technique development; temporomandibular joint syndrome; tissue engineering

DESCRIPTION (provided by applicant): A major problem confronting craniofacial repair is the difficulty in restoring soft-tissue function and contour in patients with anomalies including hemifacial microsomia, unilateral clefts of lips and palate as well as defects in the TMJ. In particular, repair of skeletal muscle defects is limited by difficulty in its transplantation and survival. A logical approach is to use existing population of muscle satellite cells which are quiescent undifferentiated precursors found beneath the basement membrane of mature muscle fibers. Following injury, activated satellite cells regenerate muscle after initiating a differentiation program whereby they migrate along laminin-rich basement membrane, proliferate, differentiate, and integrate with preexisting myofibers. Recent evidence supports the notion that satellite cells are heterogeneous and have stem cell potential. We have shown that the laminin-binding alpha 7 integrin, which is important for myoblast migration, is expressed on a subset of satellite cells and is upregulated in terminally differentiated myotubes. In this application, we propose to examine the potential of using alpha 7-positive human satellite cells for direct repair of muscle defects. We will explore the hypothesis that alpha 7 expressing satellite cells are pluripotent stem cells capable of regenerating skeletal muscle and other tissue such as bone. The proposal represents three aims. In aim 1 we will characterize human muscle-derived satellite cells and correlate expression of alpha 7 integrin with their differentiation potential for skeletal muscle and other tissue lineages. Aim 2 will determine the expression and function of the alpha 7 integrin during human skeletal muscle development. Aim 3 is focused on the use of alpha 7-expressing human skeletal muscle stem cells to engineer in vitro three-dimensional skeletal muscle myofibers. These studies will form the basis for strategies that target the mechanical reintegration of regenerating myotubes to repair orofacial muscle structures using adult skeletal muscle stem cells.

描述（由申请人提供）：颅面修复面临的一个主要问题是难以恢复软组织功能和轮廓的异常患者，包括半侧面部矮小，单侧唇腭裂以及颞下颌关节缺陷。 特别是，骨骼肌缺损的修复受到其移植和存活困难的限制。 一个合乎逻辑的方法是使用现有的肌肉卫星细胞群，这些细胞是在成熟肌纤维的基底膜下发现的静止的未分化的前体细胞。 损伤后，激活的卫星细胞在启动分化程序后再生肌肉，从而它们沿着富含层粘连蛋白的基底膜迁移，增殖，分化并与预先存在的肌纤维整合。 最近的证据支持卫星细胞是异质的并且具有干细胞潜能的概念。 我们已经表明，层粘连蛋白结合α 7整合素，这是重要的成肌细胞迁移，卫星细胞的子集上表达，并在终末分化肌管上调。 在本申请中，我们建议研究使用α 7阳性人类卫星细胞直接修复肌肉缺陷的潜力。 我们将探讨的假设，α 7表达卫星细胞是多能干细胞能够再生骨骼肌和其他组织，如骨。 该提案代表了三个目标。 在目标1中，我们将描述人肌源性卫星细胞的特征，并将α 7整合素的表达与其骨骼肌和其他组织谱系的分化潜能相关联。 目的2：研究α 7整合素在人骨骼肌发育过程中的表达和功能。 目的3是利用表达α 7的人骨骼肌干细胞体外构建三维骨骼肌肌纤维。 这些研究将为利用成人骨骼肌干细胞修复口面部肌肉结构的再生肌管机械再整合策略奠定基础。