Cezar Christine A, Mooney David J
Harvard School of Engineering and Applied Sciences, 29 Oxford Street, Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering, 60 Oxford Street, Suite 403, Cambridge, MA, 02138, USA.
Harvard School of Engineering and Applied Sciences, 29 Oxford Street, Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering, 60 Oxford Street, Suite 403, Cambridge, MA, 02138, USA.
Adv Drug Deliv Rev. 2015 Apr;84:188-97. doi: 10.1016/j.addr.2014.09.008. Epub 2014 Sep 28.
Skeletal muscle possesses a remarkable capacity for regeneration in response to minor damage, but severe injury resulting in a volumetric muscle loss can lead to extensive and irreversible fibrosis, scarring, and loss of muscle function. In early clinical trials, the intramuscular injection of cultured myoblasts was proven to be a safe but ineffective cell therapy, likely due to rapid death, poor migration, and immune rejection of the injected cells. In recent years, appropriate therapeutic cell types and culturing techniques have improved progenitor cell engraftment upon transplantation. Importantly, the identification of several key biophysical and biochemical cues that synergistically regulate satellite cell fate has paved the way for the development of cell-instructive biomaterials that serve as delivery vehicles for cells to promote in vivo regeneration. Material carriers designed to spatially and temporally mimic the satellite cell niche may be of particular importance for the complete regeneration of severely damaged skeletal muscle.
骨骼肌具有在受到轻微损伤时进行再生的显著能力,但导致肌肉体积丧失的严重损伤会导致广泛且不可逆的纤维化、瘢痕形成以及肌肉功能丧失。在早期临床试验中,肌肉注射培养的成肌细胞被证明是一种安全但无效的细胞疗法,这可能是由于注射细胞的快速死亡、迁移能力差以及免疫排斥反应。近年来,合适的治疗细胞类型和培养技术提高了祖细胞移植后的植入效率。重要的是,几种协同调节卫星细胞命运的关键生物物理和生化信号的识别,为开发具有细胞指导作用的生物材料铺平了道路,这些生物材料可作为细胞的递送载体,促进体内再生。设计用于在空间和时间上模拟卫星细胞微环境的材料载体,对于严重受损骨骼肌的完全再生可能尤为重要。