L. A. Scrimgeour1, B. A. Potz1, V. I. Pavlov1, A. Y. Gorvitovskaia1, B. Colantuono1, N. R. Sodha1, R. Abid1, F. W. Sellke1 1Brown University School Of Medicine,Cardiothoracic Surgery,Providence, RI, USA
Introduction:
Stem cell secretions of microvesicles are an enticing approach to treatment of chronic myocardial ischemia. Microvesicles influence intrinsic responses to injury via transfer of miRNAs, mRNA, siRNA, and proteins. We use intramyocardial injection of microvesicles isolated from human bone marrow-derived mesenchymal stem cells (hMSC) into ischemic swine myocardium to evaluate their effect on intrinsic repair mechanisms to treat chronic ischemia.
Methods:
Microvesicles were isolated from cultured hSMC. Seventeen Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex artery to induce localized myocardial ischemia. They were then divided into two groups; control (n=7) or microvesicle-injected group (n=10). The treatment group underwent injection of microvesicles into the ischemic myocardium two weeks after ameroid placement. Seven weeks after ameroid placement, during the swine heart harvest, plasma was collected, pooled and analyzed using a cytokine array.
Results:
Microvesicle injection into the myocardium induced systemic inflammatory changes, as seen by evaluating cytokines in peripheral blood samples. The group who received microvesicles demonstrated a significant increase in angiogenin, ENA-78, GRO, GRO-α, I-309, IL-1α, IL-1β, IL-4, IL-5, IL-15, IFN-γ, MCP-1,2,3, MCSF, MDC, MIG, TGF-β1, TNF-α, and TNF-β when compared to the control group [Figure 1, p<0.05 for all]. GCSF levels, in contrast, were decreased in the microvesicle group (p<0.05).
Conclusion:
Treatment of chronic myocardial ischemia with microvesicles derived from hSMC is an exciting application of stem cell therapy that precludes the risks of direct cell injection. Microvesicles have been suggested to not only circulate peripherally but also to be able to hone to areas of damage. In this study, we demonstrate that direct injection into the ischemic myocardium affects systemic circulation of cytokines, suggesting a powerful effect of microvesicles in stimulating existing intrinsic pathways of regeneration and repair.
