Abstract 3839: Human Mesenchymal Stem Cells Secrete an Angiogenic Proteome That Stimulates Angiogenesis in vitro and in vivo and Improves Cardiac Function Following Myocardial Infarction
BACKGROUND: Recent studies suggest that therapeutic effects of stem cell transplantation following myocardial infarction (MI) are mediated by paracrine factors. One of the main goals in the treatment of ischemic heart disease is to stimulate vascular repair mechanisms to achieve adequate myocardial perfusion. In this study we sought to explore the therapeutic angiogenic potential of mesenchymal stem cell (MSC) secretion.
METHODS AND RESULTS: MSC secretion was collected as conditioned medium (CM) using a clinically compliant protocol without using serum, feeder cells or virus transduction. MSC-CM was subjected to proteomic analysis by liquid chromatography-mass spectometry and antibody arrays. Pathway analysis of the proteome revealed potential angiogenic pathways. An in vitro assay of HUVEC spheroids confirmed the angiogenic potential of MSC-CM (3.08±0.26 [non-CM, NCM] vs. 9.08±0.61 [MSC-CM] sprouts/spheroid; p=0.001). Subsequently, a highly translational large animal model of myocardial infarction was used to assess the therapeutic applicability of MSC-CM. Pigs were subjected to surgical left circumflex coronary artery ligation and randomized to intravenous MSC-CM treatment or NCM treatment for 7 days. Three weeks after MI, capillary density was higher in border areas of pigs treated with MSC-CM (645±114 [NCM] vs. 981±55 capillaries/mm2 [MSC-CM]; p=0.021), which was accompanied by reduced myocardial infarct size (11.6±2.0 % [NCM] vs. 16.6±1.2 % [MSC-CM] of the LV; p=0.050) and preserved systolic and diastolic performance as assessed with echocardiography and pressure volume loops.
CONCLUSIONS: These data support the hypothesis that vascular repair mechanisms following myocardial MSC transplantation are mediated by paracrine mechanisms and provide evidence for the potential of MSC secretion to be exploited for treatment of ischemic heart disease.