Adult Mesenchymal Stem Cells and Derivatives in Improved Elastin Homeostasis in a Rat Model of Abdominal Aortic Aneurysms.
Adult Mesenchymal Stem Cells and Derivatives in Improved Elastin Homeostasis in a Rat Model of Abdominal Aortic Aneurysms.
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DOI：
10.1093/stcltm/szac043
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发表时间：
2022-08-23
影响因子：
6
通讯作者：
Ramamurthi, Anand
中科院分区：
文献类型：
--
作者：
Dahal, Shataakshi;Dayal, Simran;Androjna, Charlie;Peterson, John;Ramamurthi, Anand
腹主动脉瘤(AAA)是由于弹性基质的蛋白分解而形成的局限性的、易破裂的、可逆性有限的主动脉扩张。弹性基质的自然再生修复是困难的，因为成人血管平滑肌细胞(VSMCs)的弹性生成能力天生就很差。这证明有必要向AAA壁中的VSMCs提供外部的、促进弹性蛋白再生和抗蛋白降解的刺激，以恢复主动脉壁中的基质结构。将高弹性和高收缩细胞的表型引入AAA壁，能够提供这样的提示，为AAA的治疗提供了诱人的前景。在这方面，我们之前已经证明了骨髓间充质干细胞(BM-MSC)来源的SMC(CBM-SMC)具有优越的弹性原性，并且在体外能够为动脉瘤SMC提供促进弹性和抗蛋白降解的刺激。然而，与细胞治疗相关的主要问题，如它们天然地植入AAA组织的能力，它们在体内的生物分布和在AAA壁上的滞留，以及如果定位于远程组织可能对AAA组织修复过程的旁分泌影响仍不确定。因此，在这项研究中，我们重点评估了BM-MSC来源的CBM-SMCs在体内的命运、安全性和AAA修复效果。我们的结果表明，CBM-SMCs具有与未分化的BM-MSCs相似的自然归巢能力，(B)在动脉瘤样主动脉中的定位比BM-MSCs表现出更高的保留率，(C)下调AAA壁上表达的几种炎性和促凋亡细胞因子的表达，这些细胞因子有助于加速弹性基质的分解和抑制弹性纤维的新组装、修复和交联，以及(D)改善AAA壁弹性基质的含量和结构以减缓AAA的生长。我们的研究为CBM-SMC体内弹性基质修复的益处及其在逆转AAA病理生理学的细胞治疗中的应用提供了初步证据。
Abdominal aortic aneurysms (AAAs) are localized rupture-prone expansions of the aorta with limited reversibility that develop due to proteolysis of the elastic matrix. Natural regenerative repair of an elastic matrix is difficult due to the intrinsically poor elastogenicity of adult vascular smooth muscle cells (VSMCs). This justifies the need to provide external, pro-elastin regenerative- and anti-proteolytic stimuli to VSMCs in the AAA wall towards reinstating matrix structure in the aorta wall. Introducing alternative phenotypes of highly elastogenic and contractile cells into the AAA wall capable of providing such cues, proffers attractive prospects for AAA treatment. In this regard, we have previously demonstrated the superior elastogenicity of bone marrow mesenchymal stem cell (BM-MSC)-derived SMCs (cBM-SMCs) and their ability to provide pro-elastogenic and anti-proteolytic stimuli to aneurysmal SMCs in vitro. However, the major issues associated with cell therapy, such as their natural ability to home into the AAA tissue, their in vivo biodistribution and retention in the AAA wall, and possible paracrine effects on AAA tissue repair processes in the event of localization in remote tissues remain uncertain. Therefore, in this study we focused on assessing the fate, safety, and AAA reparative effects of BM-MSC-derived cBM-SMCs in vivo. Our results indicate that the cBM-SMCs (a) possess natural homing abilities similar to the undifferentiated BM-MSCs, (b) exhibit higher retention upon localization in the aneurysmal aorta than BM-MSCs, (c) downregulate the expression of several inflammatory and pro-apoptotic cytokines that are upregulated in the AAA wall contributing to accelerated elastic matrix breakdown and suppression of elastic fiber neo-assembly, repair, and crosslinking, and (d) improve elastic matrix content and structure in the AAA wall toward slowing the growth of AAAs. Our study provides initial evidence of the in vivo elastic matrix reparative benefits of cBM-SMCs and their utility in cell therapy to reverse the pathophysiology of AAAs.
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影响因子：
9.7
作者：
Dahal, Shataakshi;Swaminathan, Ganesh;Ramamurthi, Anand
通讯作者：
Ramamurthi, Anand
fibulin-4 和-5 对弹性纤维形成的差异调节。
影响因子：
4.8
作者：
Choudhury, Rawshan;McGovern, Amanda;Ridley, Caroline;Cain, Stuart A.;Baldwin, Andrew;Wang, Ming-Chuan;Guo, Chun;Mironov, Aleksandr, Jr.;Drymoussi, Zoe;Trump, Dorothy;Shuttleworth, Adrian;Baldock, Clair;Kielty, Cay M.
通讯作者：
Kielty, Cay M.
DOI：
10.1113/jp270033
发表时间：
2015-07-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Wang G;Jacquet L;Karamariti E;Xu Q
通讯作者：
Xu Q
影响因子：
6
作者：
Midha S;Jain KG;Bhaskar N;Kaur A;Rawat S;Giri S;Basu B;Mohanty S
通讯作者：
Mohanty S
影响因子：
3.3
作者：
Swaminathan, Ganesh;Gadepalli, Venkat S.;Ramamurthi, Anand
通讯作者：
Ramamurthi, Anand