Mesenchymal Stem Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Canine Chronic Ischemia Model

Abstract

Background-Bone marrow-derived stem cells are under investigation as a treatment for ischemic heart disease.Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking. Methods and Results-Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100ϫ10 6 MSCs/10 mL saline) (nϭ6) or saline only (10 mL) (controls) (nϭ6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes. Conclusions-In

Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

“…In skin cells, endothelial cells, pericytes, monocytes/macrophage, and adipocytes have been reported (24,25). However, it is currently unknown whether MSCs can differentiate into keratinocytes.…”

Endothelial cells guided by immobilized gradients of vascular endothelial growth factor on porous collagen scaffolds

“…Several cell sources have been identified and investigated for the purpose of cardiac regeneration. Some of the extensively investigated cell types include bone marrow-derives adult stem cells [7,8] and embryonic stem cells [9][10][11]. Some of the other cell types that carry some doubts in terms of their capability for the purpose of myocardial regeneration are the adipose-derived adult stem cells [12,13] and the adult skeletal myoblasts [14].…”

The Effect of Donor Variation and Senescence on Endothelial Differentiation of Human Mesenchymal Stromal Cells

“…We and others have shown that when human MSCs are grown in endothelial differentiation medium, they express endothelial markers such as CD31, von Willebrand factor and VEcadherin, both at the mRNA and protein level [11][12][13][14][15][16][17]. In addition, the actively take up acidic LDL, another hallmark of endothelial cells.…”