Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, 908 Furnas Hall, Amherst, NY 14260-4200, USA.
Cardiovasc Res. 2010 Jul 1;87(1):147-55. doi: 10.1093/cvr/cvq024. Epub 2010 Jan 22.
Bone marrow-derived smooth muscle cells (BM-SMCs) have high potential as an autologous cell source of vascular progenitors but normal cell function and turnover frequency may decline with age. In this study we set out to study the effects of organismal ageing on the molecular and functional properties of BM-SMCs.
To address this issue, we employed a smooth muscle alpha-actin promoter (alphaSMA) driving expression of enhanced green fluorescence protein (EGFP) to isolate SMCs from bone marrow of neonatal (nBM-SMCs) or adult (aBM-SMCs) sheep and examined their proliferation potential and contractility. Compared with nBM-SMCs, aBM-SMCs exhibited lower clonogenicity and proliferation potential that could be improved significantly by addition of basic fibroblast growth factor. Vascular constructs from aBM-SMCs showed reduced ability to generate force and contract fibrin hydrogels and this function could be partially restored by addition of transforming growth factor-beta1. They also exhibited lower receptor- and non-receptor-mediated vascular contractility and mechanical strength, which was comparable to that of tissue constructs prepared with vascular SMCs from neonatal umbilical veins. In agreement with the contractile properties and mechanical strength of vascular constructs, aBM-SMCs displayed significantly lower expression of alphaSMA, smoothelin, desmin, type I collagen, and tropoelastin transcripts compared with nBM-SMCs.
Understanding the effects of organismal ageing on BM-SMCs and the properties of the resulting vascular constructs may lead to innovative ways to facilitate application of these cells in the treatment of cardiovascular disease which is especially prevalent in the elderly.
骨髓源性平滑肌细胞（BM-SMCs）作为血管祖细胞的自体细胞来源具有很大的潜力，但正常细胞的功能和更替频率可能随年龄的增长而下降。在这项研究中，我们着手研究机体衰老对 BM-SMCs 分子和功能特性的影响。
为了解决这个问题，我们利用平滑肌α-肌动蛋白启动子（alphaSMA）驱动增强型绿色荧光蛋白（EGFP）的表达，从新生（nBM-SMCs）或成年（aBM-SMCs）绵羊的骨髓中分离 SMCs，并研究其增殖潜能和收缩性。与 nBM-SMCs 相比，aBM-SMCs 的克隆形成率和增殖潜能较低，通过添加碱性成纤维细胞生长因子可显著提高。aBM-SMCs 构建的血管结构产生力和收缩纤维蛋白水凝胶的能力降低，通过添加转化生长因子-β1 可部分恢复这种功能。它们还表现出较低的受体和非受体介导的血管收缩性和机械强度，与从新生脐静脉分离的血管平滑肌细胞制备的组织构建物相当。与血管构建物的收缩特性和机械强度一致，aBM-SMCs 的 alphaSMA、smoothelin、结蛋白、I 型胶原和原肌球蛋白转录本的表达明显低于 nBM-SMCs。
了解机体衰老对 BM-SMCs 的影响以及由此产生的血管构建物的特性，可能会为促进这些细胞在治疗心血管疾病中的应用提供新的方法，而心血管疾病在老年人中尤为普遍。
