Medistem Inc., San Diego, CA 92122, USA.
Cell Immunol. 2010;260(2):75-82. doi: 10.1016/j.cellimm.2009.10.006.
Duchenne muscular dystrophy (DMD) is a lethal X-linked musculodegenerative condition consisting of an underlying genetic defect whose manifestation is augmented by inflammatory mechanisms. Previous treatment approaches using gene replacement, exon-skipping or allogeneic cell therapy have been relatively unsuccessful. The only intervention to mediate improvement in survival, albeit minor, is glucocorticoid treatment. Given this modality appears to function via suppression of underlying inflammation; we focus this review on the inflammatory response as a target for mesenchymal stem cell (MSC) therapy. In contrast to other cell based therapies attempted in DMD, MSC have the advantages of (a) ability to fuse with and genetically complement dystrophic muscle; (b) possess anti-inflammatory activities; and (c) produce trophic factors that may augment activity of endogenous repair cells. We conclude by describing one practical scenario of stem cell therapy for DMD.
杜氏肌营养不良症(DMD)是一种致命的 X 连锁肌肉退行性疾病,其根本病因是遗传缺陷,炎症机制使其恶化。此前,人们尝试采用基因替换、外显子跳跃或同种异体细胞疗法进行治疗,但效果并不理想。唯一能改善患者生存情况(尽管只是轻微改善)的方法是使用糖皮质激素进行治疗。鉴于这种治疗方法似乎是通过抑制潜在炎症起作用的,我们将重点放在炎症反应上,探讨其是否可以作为间充质干细胞(MSC)治疗的靶点。与 DMD 中尝试的其他基于细胞的疗法相比,MSC 具有以下优势:(a)能够与萎缩的肌肉融合并进行基因互补;(b)具有抗炎活性;以及(c)产生的营养因子可以增强内源性修复细胞的活性。最后,我们将描述一种用于 DMD 治疗的干细胞疗法的实际方案。