School of Engineering and Applied Sciences, Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Biomaterials. 2011 Dec;32(34):8905-14. doi: 10.1016/j.biomaterials.2011.08.019. Epub 2011 Sep 10.
Many cell types of therapeutic interest, including myoblasts, exhibit reduced engraftment if cultured prior to transplantation. This study investigated whether polymeric scaffolds that direct cultured myoblasts to migrate outwards and repopulate the host damaged tissue, in concert with release of angiogenic factors designed to enhance revascularizaton of the regenerating tissue, would enhance the efficacy of this cell therapy and lead to functional muscle regeneration. This was investigated in the context of a severe injury to skeletal muscle tissue involving both myotoxin-mediated direct damage and induction of regional ischemia. Local and sustained release of VEGF and IGF-1 from macroporous scaffolds used to transplant and disperse cultured myogenic cells significantly enhanced their engraftment, limited fibrosis, and accelerated the regenerative process. This resulted in increased muscle mass and, improved contractile function. These results demonstrate the importance of finely controlling the microenvironment of transplanted cells in the treatment of severe muscle damage.
许多具有治疗意义的细胞类型,包括成肌细胞,如果在移植前进行培养,其植入效果会降低。本研究探讨了是否可以使用聚合物支架来引导培养的成肌细胞向外迁移并重新填充宿主受损组织,同时释放设计用于增强再生组织再血管化的血管生成因子,从而提高这种细胞疗法的效果,并导致功能性肌肉再生。本研究是在涉及肌毒素介导的直接损伤和区域缺血诱导的严重骨骼肌组织损伤的背景下进行的。用于移植和分散培养的成肌细胞的大孔支架局部和持续释放 VEGF 和 IGF-1 可显著提高其植入效果,限制纤维化,并加速再生过程。这导致肌肉质量增加和收缩功能改善。这些结果表明,在严重肌肉损伤的治疗中,精细控制移植细胞的微环境非常重要。