Pro-elastogenic effects of bonemarrowmesenchymal stem cell-derived smooth muscle cells on cultured aneurysmal smooth muscle cells
Pro-elastogenic effects of bonemarrowmesenchymal stem cell-derived smooth muscle cells on cultured aneurysmal smooth muscle cells
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DOI：
10.1002/term.1964
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发表时间：
2017-03-01
影响因子：
3.3
通讯作者：
Ramamurthi, Anand
中科院分区：
文献类型：
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作者：
Swaminathan, Ganesh;Gadepalli, Venkat S.;Ramamurthi, Anand
腹主动脉瘤（AAAs）涉及缓慢的蛋白质水解和结构基质成分（胶原蛋白和弹性蛋白）的损失，导致壁变薄、变弱和最终破裂。目前，没有成熟的非手术治疗方法可以减缓或阻止AAA的生长。抑制AAAs内过表达的基质金属蛋白酶（MMPs，如MMP2和-9）不足以阻止AAA的生长，因为驻留的平滑肌细胞（SMCs）弹性较差，不能克服弹性分解来恢复健康的弹性基质。为了克服这一限制，本研究试图确定大鼠骨髓间充质干细胞（BM-MSC）衍生的SMCs刺激动脉瘤性SMCs （EaRASMCs）合成和组装弹性蛋白和弹性基质的实用性。BM-MSCs成功分化为SMC细胞系（smlc）。我们的研究表明，bm - msc衍生的smlc分泌营养因子，这些营养因子包含在其培养物的条件培养基（CM）中，当实时暴露于EaRASMC培养物时，刺激这些弹性蛋白前体和基质沉积以及这些弹性缺陷细胞的交联，在减弱MMPs方面具有额外的好处，特别是MMP9。因此，该结果支持了基于使用bm - msc衍生的smlc的AAAs细胞治疗方案。虽然我们观察到弹性纤维的形成没有特别的改善，MMP2活性没有衰减，活性MMP2酶的量也没有增加，但我们相信这项研究证明了后续研究可以改善这些结果。未来的研究将探索从长期SMLC培养中收集的浓缩CM对earasmc的影响，并研究SMLC本身的弹性输出。版权所有：John Wiley & Sons， Ltd
Abdominal aortic aneurysms (AAAs) involve slow proteolysis and loss of structural matrix components (collagen and elastin), which lead to wall thinning, weakening and ultimate rupture. At this time, no established non-surgical therapy is available to slow or arrest AAA growth. Inhibiting matrix metalloproteases (MMPs; e.g. MMP2 and -9) overexpressed within AAAs is insufficient to arrest AAA growth, since resident smooth muscle cells (SMCs) are poorly elastogenic and cannot overcome elastolysis to reinstate a healthy elastic matrix. Towards overcoming this limitation, this first study sought to determine the utility of rat bone marrow mesenchymal stem cell (BM-MSC)derived SMCs to stimulate elastin and elastic matrix synthesis and assembly by aneurysmal SMCs (EaRASMCs). BM-MSCs were successfully differentiated into cells of an SMC lineage (SMLCs). Our study indicates that BM-MSC-derived SMLCs secrete trophic factors, contained in conditioned medium ( CM) from their cultures, that, when exposed to EaRASMC cultures in real time, stimulate elastin precursor and matrix deposition and crosslinking by these elastogenically deficient cells, with added benefits in terms of attenuating MMPs, specifically MMP9. The results thus lend support to a proposed cell therapy for AAAs, based on the use of BM-MSC-derived SMLCs. Although we observed no particular improvement in elastic fibre formation, no attenuation of MMP2 activity and increase in amounts of active MMP2 enzyme, we believe that this study justifies follow- up studies to improve upon these outcomes. Future studies will explore the effects of concentrated CM collected from long-term SMLC cultures on EaRASMCs and also investigate the elastogenic output of SMLCs themselves. Copyright (C) 2014 John Wiley & Sons, Ltd.