Neurosciences Division-Human Genetics, CHUQ Research Centre-CHUL, Quebec, Canada.
Cell Transplant. 2012;21(1):127-37. doi: 10.3727/096368911X576018. Epub 2011 Apr 29.
Duchenne muscular dystrophy (DMD) is the most frequent muscular dystrophy in children and young adults. Currently, there is no cure for the disease. The transplantation of healthy myoblasts is an experimental therapeutic strategy, since it could restore the expression of dystrophin in DMD muscles. Nevertheless, this cellular therapy is limited by immune reaction, low migration of the implanted cells, and high early cell death that could be at least partially due to anoikis. To avoid the lack of attachment of the cells to an extracellular matrix after the transplantation, which is the cause of anoikis, we tested the use of a fibrin gel for myoblast transplantation. In vitro, three concentrations of fibrinogen were compared (3, 20, and 50 mg/ml) to form a fibrin gel. A stiffer fibrin gel leads to less degradability and less proliferation of the cells. A concentration of 3 mg/ml fibrin gel enhanced the differentiation of the myoblasts earlier as a culture in monolayer. Human myoblasts were also transplanted in muscles of Rag/mdx mice in a fibrin gel or in a saline solution (control). The use of 3 mg/ml fibrin gel for cell transplantation increased not only the survival of the cells as measured after 5 days but also the number of fibers expressing dystrophin after 21 days, compared to the control. Moreover, the fibrin gel was also compared to a prosurvival cocktail. The survival of the myoblasts at 5 days was increased in both conditions compared to the control but the efficacy of the prosurvival cocktail was not significantly higher than the fibrin gel.
杜氏肌营养不良症（DMD）是儿童和青年中最常见的肌肉营养不良症。目前，这种疾病还没有治愈方法。健康成肌细胞的移植是一种实验性的治疗策略，因为它可以恢复 DMD 肌肉中肌营养不良蛋白的表达。然而，这种细胞疗法受到免疫反应、植入细胞迁移率低和早期细胞死亡的限制，这些问题至少部分是由于细胞凋亡引起的。为了避免移植后细胞因缺乏与细胞外基质的附着而发生细胞凋亡（即anoikis），我们测试了使用纤维蛋白凝胶进行成肌细胞移植。在体外，比较了三种浓度的纤维蛋白原（3、20 和 50 mg/ml）以形成纤维蛋白凝胶。纤维蛋白凝胶的刚性越大，降解性越低，细胞增殖能力越弱。浓度为 3 mg/ml 的纤维蛋白凝胶促进了成肌细胞更早的分化，作为单层培养物。人成肌细胞也被移植到 Rag/mdx 小鼠的肌肉中，一种是纤维蛋白凝胶，另一种是生理盐水（对照）。与对照组相比，使用 3 mg/ml 的纤维蛋白凝胶进行细胞移植不仅增加了细胞在 5 天后的存活率，而且还增加了 21 天后表达肌营养不良蛋白的纤维数量。此外，还将纤维蛋白凝胶与一种促进生存的鸡尾酒进行了比较。与对照组相比，两种情况下的成肌细胞在 5 天后的存活率都有所提高，但促进生存的鸡尾酒的效果并不明显优于纤维蛋白凝胶。
