SKELETAL MUSCLE STEM CELLS FOR TISSUE REPAIR

用于组织修复的骨骼肌干细胞

• 批准号: 7067183
• 负责人: RANDALL H KRAMER
• 金额: $ 33.29万
• 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 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067183
• 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（申请人提供）：颅面修复面临的一个主要问题是，患有半面部短小症、单侧唇腭裂以及颞下颌关节缺陷等异常的患者，其软组织功能和轮廓难以恢复。 特别是骨骼肌缺陷的修复因其移植和存活困难而受到限制。 一种合乎逻辑的方法是使用现有的肌肉卫星细胞群，这些卫星细胞是在成熟肌纤维的基底膜下发现的静止的未分化前体细胞。 受伤后，激活的卫星细胞在启动分化程序后再生肌肉，它们沿着富含层粘连蛋白的基底膜迁移、增殖、分化并与先前存在的肌纤维整合。 最近的证据支持卫星细胞是异质的并且具有干细胞潜力的观点。 我们已经证明，对于成肌细胞迁移很重要的层粘连蛋白结合α7整合素在卫星细胞的子集上表达，并且在终末分化的肌管中表达上调。 在此应用中，我们建议研究使用 α7 阳性人类卫星细胞直接修复肌肉缺陷的潜力。 我们将探讨以下假设：表达 α7 的卫星细胞是能够再生骨骼肌和其他组织（例如骨骼）的多能干细胞。 该提案代表了三个目标。 在目标 1 中，我们将表征人类肌肉来源的卫星细胞，并将 α7 整合素的表达与其骨骼肌和其他组织谱系的分化潜力相关联。 目标 2 将确定 α7 整合素在人类骨骼肌发育过程中的表达和功能。 目标 3 的重点是使用表达 α 7 的人类骨骼肌干细胞来设计体外三维骨骼肌肌纤维。 这些研究将为针对再生肌管的机械重新整合以利用成体骨骼肌干细胞修复口面肌结构的策略奠定基础。

项目成果

Analysis of human muscle stem cells reveals a differentiation-resistant progenitor cell population expressing Pax7 capable of self-renewal.

对人类肌肉干细胞的分析揭示了表达具有自我更新能力的 Pax7 的抗分化祖细胞群。

• 发表时间: 2009-01
• 作者: Pawlikowski, Bradley;Lee, Laimeng;Zuo, Jianhong;Kramer, Randall H
• 通讯作者: Kramer, Randall H

Alpha7 integrin expression is negatively regulated by deltaEF1 during skeletal myogenesis.

在骨骼肌生成过程中，α7 整合素表达受到 deltaEF1 的负向调节。

• 发表时间: 2005-10-28
• 作者: Jethanandani, Poonam;Kramer, Randall H
• 通讯作者: Kramer, Randall H

Modulation of satellite cell adhesion and motility following BMP2-induced differentiation to osteoblast lineage.

BMP2 诱导分化为成骨细胞谱系后卫星细胞粘附和运动的调节。

• 发表时间: 2007-02-02
• 影响因子: 3.1
• 作者: Ozeki, Nobuaki;Jethanandani, Poonam;Nakamura, Hiroshi;Ziober, Barry L;Kramer, Randall H
• 通讯作者: Kramer, Randall H

alpha7 integrin expressing human fetal myogenic progenitors have stem cell-like properties and are capable of osteogenic differentiation.

表达α7整合素的人类胎儿肌原祖细胞具有干细胞样特性，并且能够成骨分化。

• 发表时间: 2006-12-10
• 影响因子: 3.7
• 作者: Ozeki, Nobuaki;Lim, Moon;Yao, Chung;Tolar, Mirek;Kramer, Randall H
• 通讯作者: Kramer, Randall H

Differentiation of human skeletal muscle stem cells into odontoblasts is dependent on induction of α1 integrin expression.

人类骨骼肌干细胞向成牙本质细胞的分化依赖于α1 整合素表达的诱导。

• 发表时间: 2014
• 作者: Ozeki, Nobuaki;Mogi, Makio;Yamaguchi, Hideyuki;Hiyama, Taiki;Kawai, Rie;Hase, Naoko;Nakata, Kazuhiko;Nakamura, Hiroshi;Kramer, Randall H
• 通讯作者: Kramer, Randall H