Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611-2875.
Baxter Laboratory for Stem Cell Biology, Stanford University School of Medicine, Stanford, CA 94305-5175.
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):E7919-E7928. doi: 10.1073/pnas.1708142114. Epub 2017 Sep 5.
Muscle stem cells are a potent cell population dedicated to efficacious skeletal muscle regeneration, but their therapeutic utility is currently limited by mode of delivery. We developed a cell delivery strategy based on a supramolecular liquid crystal formed by peptide amphiphiles (PAs) that encapsulates cells and growth factors within a muscle-like unidirectionally ordered environment of nanofibers. The stiffness of the PA scaffolds, dependent on amino acid sequence, was found to determine the macroscopic degree of cell alignment templated by the nanofibers in vitro. Furthermore, these PA scaffolds support myogenic progenitor cell survival and proliferation and they can be optimized to induce cell differentiation and maturation. We engineered an in vivo delivery system to assemble scaffolds by injection of a PA solution that enabled coalignment of scaffold nanofibers with endogenous myofibers. These scaffolds locally retained growth factors, displayed degradation rates matching the time course of muscle tissue regeneration, and markedly enhanced the engraftment of muscle stem cells in injured and noninjured muscles in mice.
肌肉干细胞是一种具有强大功效的细胞群体，专门用于有效的骨骼肌再生，但它们的治疗用途目前受到输送方式的限制。我们开发了一种基于由肽两亲物 (PAs) 形成的超分子液晶的细胞输送策略，该策略将细胞和生长因子封装在具有类似肌肉的单向有序纳米纤维环境中。发现 PA 支架的刚度取决于氨基酸序列，这决定了纳米纤维体外模板化细胞宏观排列的程度。此外，这些 PA 支架支持成肌祖细胞的存活和增殖，并且可以对其进行优化以诱导细胞分化和成熟。我们设计了一种体内输送系统，通过注射 PA 溶液来组装支架，从而使支架纳米纤维与内源性肌纤维对齐。这些支架局部保留生长因子，显示出与肌肉组织再生时间过程相匹配的降解速率，并显著增强了肌肉干细胞在受伤和未受伤肌肉中的植入。
