Allogeneic Mesenchymal Stem Cells Restore Endothelial Function in XXXX by Stimulating Endothelial Progenitor Cells.

@entity1 @entity296 @entity712 @entity7 @entity409 @entity450 @entity842
BACKGROUND: Endothelial dysfunction, characterized by diminished endothelial progenitor cell (EPC) function and @entity450 ( @entity450 ), is a clinically significant feature of @entity712 ( @entity712 ). Mesenchymal stem cells (MSCs), which have pro-angiogenic properties, have the potential to restore endothelial function. Accordingly, we tested the hypothesis that MSCs increase EPC function and restore @entity450 ( @entity450 ). METHODS: Idiopathic dilated and @entity296 @entity1 were randomly assigned to receive autologous (n  =  7) or allogeneic (n  =  15) MSCs. We assessed EPC-colony forming units (EPC-CFUs), @entity450 , and circulating levels of @entity7 ( @entity7 ) in @entity1 before and three months after MSC transendocardial injection (n  =  22) and in healthy controls (n  =  10). FINDINGS: EPC-colony forming units (CFUs) were markedly reduced in @entity712 compared to healthy controls (4      3 vs. 25      16  CFUs, P  <  0.0001). Similarly, @entity450 % was impaired in @entity712 (5.6      3.2% vs. 9.0      3.3%, P  =  0.01). Allogeneic, but not autologous, MSCs improved endothelial function three months after treatment (  10      5 vs.   1      3  CFUs, P  =  0.0067;   3.7      3% vs.   -0.46      3% @entity450 , P  =  0.005). @entity1 who received allogeneic MSCs had a reduction in serum @entity7 levels three months after treatment, while @entity1 who received autologous MSCs had an increase (P  =  0.0012), and these changes correlated with the change in EPC-CFUs (P  <  0.0001). Lastly, @entity1 umbilical vein endothelial cells (HUVECs) with impaired vasculogenesis due to pharmacologic @entity842 synthase inhibition, were rescued by allogeneic MSC conditioned medium (P  =  0.006). INTERPRETATION: These findings reveal a novel mechanism whereby allogeneic, but not autologous, MSC administration results in the proliferation of functional EPCs and improvement in vascular reactivity, which in turn restores endothelial function towards normal in @entity1 with @entity712 . These findings have significant clinical and biological implications for the use of MSCs in @entity712 and other disorders associated with @entity409 .
