Li Yong, Zhang Cheng, Xiong Fu, Yu Mei-juan, Peng Fu-Lin, Shang Yan-chang, Zhao Cui-ping, Xu Yong-feng, Liu Zheng-shan, Zhou Chang, Wu Jin-lang
Department of Neurology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ProC.
BMC Cell Biol. 2008 May 19;9:24. doi: 10.1186/1471-2121-9-24.
Human mesenchymal stem cells (MSCs) have been studied and applied extensively because of their ability to self-renew and differentiate into various cell types. Since most human diseases models are murine, mouse MSCs should have been studied in detail. The mdx mouse - a Duchenne muscular dystrophy model - was produced by introducing a point mutation in the dystrophin gene. To understand the role of dystrophin in MSCs, we compared MSCs from mdx and C57BL/10 mice, focusing particularly on the aspects of light and electron microscopic morphology, immunophenotyping, and differentiation potential.
Our study showed that at passage 10, mdx-MSCs exhibited increased heterochromatin, larger vacuoles, and more lysosomes under electron microscopy compared to C57BL/10-MSCs. C57BL/10-MSCs formed a few myotubes, while mdx-MSCs did not at the same passages. By passage 21, mdx-MSCs but not C57BL/10-MSCs had gradually lost their proliferative ability. In addition, a significant difference in the expression of CD34, not Sca-1 and CD11b, was observed between the MSCs from the 2 mice.
Our current study reveals that the MSCs from the 2 mice, namely, C57BL/10 and mdx, exhibit differences in proliferative and myogenic abilities. The results suggest that the changes in mouse MSC behavior may be influenced by lack of dystrophin protein in mdx mouse.
人间充质干细胞(MSCs)因其自我更新和分化为多种细胞类型的能力而得到广泛研究和应用。由于大多数人类疾病模型是鼠类的,因此应该对小鼠间充质干细胞进行详细研究。mdx小鼠——一种杜氏肌营养不良模型——是通过在肌营养不良蛋白基因中引入点突变产生的。为了了解肌营养不良蛋白在间充质干细胞中的作用,我们比较了mdx小鼠和C57BL/10小鼠的间充质干细胞,特别关注光镜和电镜形态学、免疫表型分析以及分化潜能等方面。
我们的研究表明,在第10代时,与C57BL/10间充质干细胞相比,mdx间充质干细胞在电镜下表现出异染色质增加、空泡更大和溶酶体更多。C57BL/10间充质干细胞形成了一些肌管,而mdx间充质干细胞在相同代次时未形成。到第21代时,mdx间充质干细胞逐渐失去了增殖能力,而C57BL/10间充质干细胞没有。此外,在这两种小鼠的间充质干细胞之间观察到CD34表达存在显著差异,而Sca-1和CD11b表达无差异。
我们目前的研究表明,C57BL/10和mdx这两种小鼠的间充质干细胞在增殖和生肌能力方面存在差异。结果表明,mdx小鼠中肌营养不良蛋白的缺乏可能影响小鼠间充质干细胞的行为变化。