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rBMSCs/ITGA5B1 Promotes Human Vascular Smooth Muscle Cell Differentiation via Enhancing Nitric Oxide Production
Int J Stem Cells 2018;11:168-176
Published online November 30, 2018;  
© 2018 Korean Society for Stem Cell Research.

Yingxin Zhang1, Jie Ding1, Cong Xu1, Hongli Yang1, Peng Xia2, Shengjun Ma2, Haiying Chen1

1Central Laboratory of Liaocheng People's Hospital, Liaocheng, Shandong, China,
2Department of Cardiology, Liaocheng People's Hospital, Liaocheng, Shandong, China
Correspondence to: Haiying Chen
Central Laboratory of Liaocheng People's Hospital, Liaocheng, Shandong 252000, China
Tel: +86-134-6576-9078, Fax: +86-635-827-6009
Shengjun Ma
Department of Cardiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China
Tel: +86-134-6576-9078, Fax: +86-635-827-2289
Received September 4, 2018; Revised September 6, 2018; Accepted October 8, 2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background and Objectives: Previous studies have shown that integrins alpha5beta1 (ITGA5B1) gene-modified rat bone marrow mesenchymal stem cells (rBMSCs) could prevent cell anoikis and increase the nitric oxide (NO) production. Here we examined the capability of rBMSCs/ITGA5B1 on the phenotype modulation of Human Pulmonary Artery Smooth Muscle Cell (HPASMC) in vitro.
Methods and Results: The synthetic (dedifferentiated) phenotype of HPASMC was induced by monocrotaline (MCT, 1µ M) for 24 h and then co-cultured with rBMSCs/ITGA5B1 in a transwell culture system. The activation of NO/cGMP (nitric oxide/Guanosine-3’, 5’-cyclic monophosphate) signaling was investigated in HPASMC. The changes of pro-inflammatory factors, oxidative stress, vasodilator, vasoconstrictor, contractile and synthetic genes, and the morphological changes of HPASMC were investigated. The results of this study showed that the NO/cGMP signal, endothelial nitric oxide synthase (eNOS) expression, the expression of the vasoprotective genes heme oxygenase-1 (HMOX1) and prostaglandin-endoperoxide synthase 2 (PTGS2) were increased, but the expression of transforming growth factor-β1 (TGFβ1), CCAAT/enhancer-binding proteins delta (Cebpd), Krüppel-like factor 4 (KLF4), and activating transcription factor 4 (ATF4) were reduced in MCT treated HPASMC co-cultured with rBMSCs/ITGA5B1. The synthetic smooth muscle cells (SMCs) phenotype markers thrombospondin-1, epiregulin and the vasoconstrictor endothelin (ET)-1, thromboxane A2 receptor (TbxA2R) were down-regulated, whereas the contractile SMCs phenotype marker transgelin expression was up-regulated by rBMSCs/ITGA5B1. Furthermore, rBMSCs/ITGA5B1 promoted the morphological restoration from synthetic (dedifferentiation) to contractile (differentiation) phenotype in MCT treated HPASMC.
Conclusions: rBMSCs/ITGA5B1 could inhibit inflammation and oxidative stress related genes to promote the HPASMC cell differentiation by activation NO/cGMP signal.
Keywords : Bone marrow derived mesenchymal stem cells, Integrin, Nitric oxide, Phenotypic transition, Human vascular smooth muscle cell (HPASMC)

November 2018, 11 (2)