Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.
Cytotherapy. 2013 Sep;15(9):1062-72. doi: 10.1016/j.jcyt.2013.03.015. Epub 2013 Jun 22.
Human bone marrow mesenchymal stromal cells are useful in regenerative medicine for various diseases, but it remains unclear whether the aging of donors alters the multipotency of these cells. In this study, we examined age-related changes in the chondrogenic, osteogenic and adipogenic potential of mesenchymal stromal cells from 17 donors (25-81 years old), including patients with or without systemic vascular diseases.
All stem cell lines were expanded with fibroblast growth factor-2 and then exposed to differentiation induction media. The chondrogenic potential was determined from the glycosaminoglycan content and the SOX9, collagen type 2 alpha 1 (COL2A1) and aggrecan (AGG) messenger RNA levels. The osteogenic potential was determined by monitoring the alkaline phosphatase activity and calcium content, and the adipogenic potential was determined from the glycerol-3-phosphate dehydrogenase activity and oil red O staining.
Systemic vascular diseases, including arteriosclerosis obliterans and Buerger disease, did not significantly affect the trilineage differentiation potential of the cells. Under these conditions, all chondrocyte markers examined, including the SOX9 messenger RNA level, showed age-related decline, whereas none of the osteoblast or adipocyte markers showed age-dependent changes.
The aging of donors from young adult to elderly selectively decreased the chondrogenic potential of mesenchymal stromal cells. This information will be useful in stromal cell-based therapy for cartilage-related diseases.
人类骨髓间充质基质细胞在各种疾病的再生医学中具有重要作用，但供体的衰老是否改变这些细胞的多能性仍不清楚。在这项研究中，我们检查了来自 17 名供体（25-81 岁）的间充质基质细胞的软骨形成、成骨和脂肪形成潜能的年龄相关变化，包括患有或不患有系统性血管疾病的患者。
所有干细胞系均用成纤维细胞生长因子-2 扩增，然后暴露于分化诱导培养基中。通过测定糖胺聚糖含量以及 SOX9、胶原类型 2 阿尔法 1（COL2A1）和聚集蛋白（AGG）信使 RNA 水平来确定软骨形成潜能。通过监测碱性磷酸酶活性和钙含量来确定成骨潜能，通过甘油-3-磷酸脱氢酶活性和油红 O 染色来确定脂肪形成潜能。
包括动脉硬化闭塞症和伯格病在内的系统性血管疾病并没有显著影响细胞的三系分化潜能。在这些条件下，所有检查的软骨细胞标志物，包括 SOX9 信使 RNA 水平，均表现出与年龄相关的下降，而没有任何成骨细胞或脂肪细胞标志物表现出与年龄相关的变化。
从年轻成年到老年的供体衰老选择性地降低了间充质基质细胞的软骨形成潜能。这些信息将对基于基质细胞的软骨相关疾病治疗有用。
