MMP‐2 and MT1‐MMP Silencing Induces the Differentiation of Porcine Adipose‐Derived Mesenchymal Stem Cells to Endothelial Cells

Abstract

Rationale: The molecular mechanisms that control the ability of adipose-derived mesenchymal stem cells (ADMSCs) to remodel 3-dimensional extracellular matrix barriers during differentiation are not clearly understood. Herein, we studied the expression of matrix metalloproteinases (MMPs) during the differentiation of AMSCs to endothelial cells (ECs). Methods: MSCs were isolated from porcine abdominal adipose tissue, and characterized by CD44+, CD90+, CD105+, CD14-, and CD45-. The plasticity of AMSCs was detected by multi-lineage differentiation. The mRNA transcripts, protein expression of EC marker, MMPs and TIMPs, and enzyme activity of MMP-2 were analyzed. Results: The differentiation of ADMSCs to ECs was confirmed by protein and mRNA expression of EC markers. The mRNA transcripts for MMP-2 and MT1-MMP were significantly increased during the differentiation. Western blot, zymography and ELISA showed an elevated MMP-2 and MT1-MMP expression and activity. MMP2 and MT1-MMP silencing showed significant increase in the expression of EC markers, formation of capillary tubes, and acetylated-LDL uptake. Conclusion We, for the first time, report that the up-regulation of MMP2 and MT1-MMP has an inhibitory effect on the differentiation of AMSCs to ECs, and silencing these MMPs can induce the differentiation. These findings could have significant clinical impact in developing better therapeutic approaches to re-endothelialize coronary arteries following interventional procedures or inducing angiogenesis to regenerate myocardium.