Angiogenic and Restorative Abilities of Human Mesenchymal Stem Cells Were Reduced Following Treatment With Serum From Diabetes Mellitus Type 2 Patients

This experiment investigated the impact of serum from patients with type 2 diabetes mellitus on the angiogenic behavior of human mesenchymal stem cells in vitro. Changes in the level of Ang-1, Ang-2, cell migration, and trans-differentiation into pericytes and endothelial lineage were monitored after 7 days. The interaction of mesenchymal stem cells with endothelial cells were evaluated using surface plasmon resonance technique. Paracrine restorative effect of diabetic stem cells was tested on pancreatic β cells. Compared to data from FBS and normal serum, diabetic serum reduced the stem cell survival and chemotaxis toward VEGF and SDF-1α (P < 0.05). Diabetic condition were found to decline cell migration rate and the activity of MMP-2 and -9 (P < 0.05). The down-regulation of VEGFR-2 and CXCR-4 was observed with an increase in the level of miR-1-3p and miR-15b-5p at the same time. The paracrine angiogenic potential of diabetic stem cells was disturbed via the changes in the dynamic of Ang-1, Ang-2, and VEGF. Surface plasmon resonance analysis showed that diabetes could induce an aberrant increase in the interaction of stem cells with endothelial cells. After treatment with diabetic serum, the expression of VE-cadherin and NG2 and ability for uptake of Dil-Ac-LDL were reduced (P < 0.01). Conditioned media prepared from diabetic stem cells were unable to decrease fatty acid accumulation in β-cells (P < 0.05). The level of insulin secreted by β-cells was not affected after exposure to supernatant from diabetic or non-diabetic mesenchymal stem cells. Data suggest diabetes could decrease angiogenic and restorative effect of stem cells in vitro.

Publication year: 2017
Authors: Rezaie J. 1, Mehranjani M.S. 1, Rahbarghazi R. 2,3, Shariatzadeh M.A. 1

1 – Department of Biology, Faculty of Sciences, Arak University, Arak, Iran
2 – Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3 – Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Published in: Journal of Cellular Biochemistry, 2017, 9999, p. 1-12
DOI: 10.1002/jcb.26211


diabetic serum FBS (serum-supplement as control) human bone marrow MSC cell line (hMSC) human umbilical vascular endothelial cells (HUVEC) HUVEC cell monolayer grown ex situ interaction of stem cells with endothelial cells non-diabetic serum stem cells grown in different environments


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