Engineering A Biomaterial Niche of Satellite Cells for Skeletal Muscle Regeneration

 描述(申请人提供)：用于骨骼肌再生的卫星细胞的生物利基在轻微损伤后，骨骼肌表现出显著的再生能力，卫星细胞(SCs)是一种干细胞群体，位于基板下的肌肉纤维表面。然而，在创伤、手术或疾病导致的严重肌肉损伤的情况下，这种自然愈合过程不会发生。由于损伤肌肉缺乏适当的支持性微环境，移植细胞存活率低，移植细胞长期植入，功能改善有限，阻碍了目前基于细胞的治疗。因此，迫切需要开发一种生物工程策略，为新的功能肌肉的再生提供细胞和结构支持。干细胞小生境提供了一个局部微环境，其中充满了复杂的信号网络，调控干细胞的自我更新、增殖和肌源性分化。这项提案的目标是开发一种生物工程细胞利基产品 为干细胞提供适当的结构和机械支持，以促进肌肉再生。我们的目标将通过执行以下具体目标来实现：目标1：创建一个由排列的纤维基质组成的聚合物平台，模拟肌肉组织的各向异性组织。目的2：优化支架的性能，重点研究支架纤维的直径和硬度，以增强细胞的反应，包括干细胞的附着、自我更新、增殖和分化。目的：评价干细胞接种于优化的纤维支架上支持肌肉再生的体内再生效果。我们的总体假设是，具有适当结构和机械性能的合成支架将作为支持干细胞加速肌肉再生的生物工程利基。该项目的成功完成将有助于了解干细胞的生物材料调节，并为开发有效的肌肉再生装置治疗肌肉疾病铺平道路。

 DESCRIPTION (provided by applicant): A Biomaterial Niche of Satellite Cells for Skeletal Muscle Regeneration In response to minor injuries, skeletal muscles exhibit a remarkable regenerative capacity empowered by satellite cells (SCs), a stem cell population localized along the surface of muscle fibers under the basal lamina. However, in the case of severe muscle injuries resulting from trauma, surgery, or disease, this natural healing process does not occur. Current cell-based therapies are hindered by limited functional improvement resulting from low survival and long-term engraftment of the transplanted cells due to the lack of appropriate supportive microenvironment in the injured muscle. Thus, there is a critical need for the development of a bioengineering strategy to provide cellular and structural support in regeneration of new functional muscles. SC niche provides a local microenvironment imbued with a complex network of signals that regulate the self-renewal, proliferation, and myogenic differentiation of SCs. The goal of this proposal is to develop a bioengineered cell niche offering appropriate structural and mechanical support for SCs to facilitate muscle regeneration. Our goal will be achieved by performing the following specific aims: Aim 1: To create a polymeric platform of aligned fiber matrices mimicking anisotropic organization of muscular tissue. Aim 2: To optimize scaffold properties with a focus on scaffold fiber diameter and stiffness to enhance cellular responses including attachment, self-renewal, proliferation, and differentiation of SCs. Aim 3: To evaluate the in vivo regenerative efficacy of the SCs seeded on the optimized fiber scaffold in supporting muscle regeneration. Our overall hypothesis is that a synthetic scaffold with appropriate structural and mechanical properties will act as a bioengineered niche to support SCs for accelerated muscle regeneration. Successful completion of the project will provide an understanding of the biomaterial regulation of SCs and pave the way for the development of an effective muscle regenerative device to treat muscular diseases.