Engineering A Biomaterial Niche of Satellite Cells for Skeletal Muscle Regeneration

 描述（由申请人提供）：用于骨骼肌再生的卫星细胞的生物材料小生境对于轻微损伤，骨骼肌表现出由卫星细胞（SC）赋予的显著再生能力，卫星细胞（SC）是一种干细胞群，其沿着基底层下的肌纤维表面定位。然而，在由创伤、手术或疾病引起的严重肌肉损伤的情况下，这种自然愈合过程不会发生。目前的基于细胞的治疗受到有限的功能改善的阻碍，这是由于受损肌肉中缺乏适当的支持性微环境，移植细胞的存活率低和长期植入造成的。因此，迫切需要开发一种生物工程策略，以在新功能肌肉的再生中提供细胞和结构支持。SC生态位提供了一个局部微环境，充满了复杂的信号网络，调节SC的自我更新，增殖和肌源性分化。该提案的目标是开发一种生物工程细胞利基， 为SC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：创建模拟肌肉组织的各向异性组织的对齐纤维基质的聚合物平台。目标二：优化支架性能，重点关注支架纤维直径和刚度，以增强细胞反应，包括SC的附着、自我更新、增殖和分化。目的3：评价在优化的纤维支架上种植的干细胞在体内支持肌肉再生的效果。我们的总体假设是，具有适当结构和机械特性的合成支架将作为生物工程利基来支持SC加速肌肉再生。该项目的成功完成将提供对SC生物材料调节的理解，并为开发有效的肌肉再生装置以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.