Molecular and functional effects of organismal ageing on smooth muscle cells derived from bone marrow mesenchymal stem cells
Molecular and functional effects of organismal ageing on smooth muscle cells derived from bone marrow mesenchymal stem cells
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DOI：
10.1093/cvr/cvq024
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发表时间：
2010-07-01
影响因子：
10.8
通讯作者：
Andreadis, Stelios T.
中科院分区：
文献类型：
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作者：
Han, Juhee;Liu, Jin Yu;Andreadis, Stelios T.
骨髓来源的平滑肌细胞(BM-SMCs)作为血管前体细胞的自体来源具有很高的潜力，但正常细胞功能和周转频率可能会随着年龄的增长而下降。本研究旨在研究生物老化对BM-SMCs分子和功能特性的影响。为了解决这个问题，我们使用了一种平滑肌α-肌动蛋白启动子(α-SMA)来驱动增强型绿色荧光蛋白(EGFP)的表达，从新生绵羊(NBM-SMCs)或成年绵羊(ABM-SMCs)的骨髓中分离出SMC，并检测了它们的增殖能力和收缩能力。与NBM-SMC相比，ABM-SMC具有较低的克隆形成能力和增殖能力，加入碱性成纤维细胞生长因子可显著提高其克隆形成能力和增殖能力。来自ABM-SMCs的血管构造物产生力量和收缩纤维蛋白水凝胶的能力降低，加入转化生长因子-β1可以部分恢复这一功能。它们还表现出较低的受体和非受体介导的血管收缩和机械强度，与来自新生儿脐静脉的血管SMCs制备的组织构造物相当。与血管构造物的收缩特性和机械强度一致，ABM-SMC的α-SMA、平滑蛋白、结蛋白、I型胶原和原弹性蛋白转录本的表达显著低于NBM-SMC。了解生物老化对BM-SMC的影响以及由此产生的血管构造物的特性可能导致促进这些细胞应用于治疗心血管疾病的创新方法，而心血管疾病在老年人中尤其普遍。
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 (alpha SMA) 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-beta 1. 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 alpha SMA, 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.