Asumda Faizal Z, Chase P Bryant
Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, USA.
BMC Cell Biol. 2011 Oct 12;12:44. doi: 10.1186/1471-2121-12-44.
The efficacy of adult stem cells is known to be compromised as a function of age. This therefore raises questions about the effectiveness of autologous cell therapy in elderly patients.
We demonstrated that the expression profile of stemness markers was altered in BM-MSCs derived from old rats. BM-MSCs from young rats (4 months) expressed Oct-4, Sox-2 and NANOG, but we failed to detect Sox-2 and NANOG in BM-MSCs from older animals (15 months). Chondrogenic, osteogenic and adipogenic potential is compromised in old BM-MSCs. Stimulation with a cocktail mixture of bone morphogenetic protein (BMP-2), fibroblast growth factor (FGF-2) and insulin-like growth factor (IGF-1) induced cardiomyogenesis in young BM-MSCs but not old BM-MSCs. Significant differences in the expression of gap junction protein connexin-43 were observed between young and old BM-MSCs. Young and old BM-MSCs fused with neonatal ventricular cardiomyocytes in co-culture and expressed key cardiac transcription factors and structural proteins. Cells from old animals expressed significantly lower levels of VEGF, IGF, EGF, and G-CSF. Significantly higher levels of DNA double strand break marker γ-H2AX and diminished levels of telomerase activity were observed in old BM-MSCs.
The results suggest age related differences in the differentiation capacity of BM-MSCs. These changes may affect the efficacy of BM-MSCs for use in stem cell therapy.
已知成体干细胞的功效会随着年龄增长而受损。因此，这引发了关于老年患者自体细胞治疗有效性的问题。
我们证明，老年大鼠来源的骨髓间充质干细胞（BM-MSCs）中干性标志物的表达谱发生了改变。年轻大鼠（4个月）的BM-MSCs表达Oct-4、Sox-2和NANOG，但我们未能在老年动物（15个月）的BM-MSCs中检测到Sox-2和NANOG。老年BM-MSCs的软骨生成、成骨和成脂潜能受损。用骨形态发生蛋白（BMP-2）、成纤维细胞生长因子（FGF-2）和胰岛素样生长因子（IGF-1）的混合鸡尾酒刺激可诱导年轻BM-MSCs发生心肌生成，但老年BM-MSCs则不能。在年轻和老年BM-MSCs之间观察到缝隙连接蛋白连接蛋白43的表达存在显著差异。年轻和老年BM-MSCs在共培养中与新生心室心肌细胞融合，并表达关键的心脏转录因子和结构蛋白。老年动物的细胞表达的血管内皮生长因子（VEGF）、胰岛素样生长因子（IGF）、表皮生长因子（EGF）和粒细胞集落刺激因子（G-CSF）水平显著降低。在老年BM-MSCs中观察到DNA双链断裂标志物γ-H2AX水平显著升高，端粒酶活性水平降低。
结果表明BM-MSCs的分化能力存在与年龄相关差异。这些变化可能会影响BM-MSCs用于干细胞治疗的疗效。
