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人脐带间充质干细胞减轻 Sprague-Dawley 大鼠腹主动脉瘤的进展:血管平滑肌细胞表型调节的意义。

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation.

机构信息

Department of Vascular Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.

Key Laboratory of Pathogenesis, Prevention and Therapeutics of Aortic Aneurysm in Liaoning Province, Shenyang, China.

出版信息

Stem Cells Dev. 2020 Aug 1;29(15):981-993. doi: 10.1089/scd.2020.0058. Epub 2020 Jul 13.

Abstract

Abdominal aortic aneurysm (AAA) is life-threatening, for which efficient nonsurgical treatment strategy has not been available so far. Several previous studies investigating the therapeutic effect of mesenchymal stem cells (MSCs) in AAA indicated that MSCs could inhibit aneurysmal inflammatory responses and extracellular matrix destruction, and suppress aneurysm occurrence and expansion. Vascular smooth muscle cell (VSMC) phenotypic plasticity is reported to be predisposed in AAA initiation and progression. However, little is known about the effect of MSCs on VSMC phenotypic modulation in AAA. In this study, we investigate the therapeutic efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) in elastase-induced AAA model and evaluate the effect of UC-MSC on VSMC phenotypic regulation. We demonstrate that the intravenous injection of UC-MSC attenuates elastase-induced aneurysmal expansion, reduces elastin degradation and fragmentation, inhibits MMPs and TNF-α expression, and preserves and/or restores VSMC contractile phenotype in AAA. Taken together, these results highlight the therapeutic and VSMC phenotypic modulation effects of UC-MSC in AAA progression, which further indicates the potential of applying UC-MSC as an alternative treatment candidate for AAA.

摘要

腹主动脉瘤(AAA)是一种危及生命的疾病,目前还没有有效的非手术治疗策略。几项先前研究调查了间充质干细胞(MSCs)在 AAA 中的治疗效果,表明 MSCs 可以抑制动脉瘤炎症反应和细胞外基质破坏,并抑制动脉瘤的发生和扩张。血管平滑肌细胞(VSMC)表型可塑性被认为是 AAA 发生和进展的主要因素。然而,关于 MSCs 对 AAA 中 VSMC 表型调节的影响知之甚少。在本研究中,我们研究了脐带间充质干细胞(UC-MSCs)在弹性蛋白酶诱导的 AAA 模型中的治疗效果,并评估了 UC-MSC 对 VSMC 表型调节的影响。我们证明,UC-MSC 的静脉注射可减轻弹性蛋白酶诱导的动脉瘤扩张,减少弹性蛋白降解和碎片化,抑制 MMPs 和 TNF-α 的表达,并在 AAA 中保存和/或恢复 VSMC 收缩表型。综上所述,这些结果强调了 UC-MSC 在 AAA 进展中的治疗和 VSMC 表型调节作用,进一步表明应用 UC-MSC 作为 AAA 的替代治疗候选物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c68/7410303/75fb2df0dd4e/scd.2020.0058_figure1.jpg

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