Peer-Reviewed Journal Details
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Flynn AW, Chen X, O'Connell E, O'Brien T
Stem Cell Research & Therapy
A comparison of the efficacy of transplantation of bone marrow derived mesenchymal stem cells and unrestricted somatic stem cells on outcome after acute myocardial infarction.
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Cardiac Failure Cardiac Repair Guiding Mesenchymal Stem Cell Myocardial Infarction Pre-Conditioned Stem Cell Umbilical Cord Unrestricted Somatic Stem Cell
Introduction: A number of questions remain unanswered in the field of cell therapy foracute myocardial infarction (MI), including what is the optimal cell type, and can therapeutic efficacy be enhanced by conditioning regimens. In this study, we sought to address these questions by directly comparing the effect of bone marrow-derived mesenchymal stem cells (MSC) and unrestricted somatic stem cells (USSC) delivered 24 hours post MI and by determining if the therapeutic efficacy of USSC could be enhanced by exposing the cells to guiding factors before cell transplantation.Methods: USSC were guided by exposure to 50ng/ml bFGF, 20ng/ml HGF and 20ng/ml BMP2 for 24 hours. Using a Sprague-Dawley rat model of acute MI, we transplanted cells by intramyocardial injection 24 hours post-MI. Cardiac function was serially measured using echocardiography and histological analyses of infarct morphology,angiogenesis and apoptosis were obtained. Using microarray and real-time quantitative PCR, transcriptomic and proteomic changes were assessed.Results: At 28 days post-MI, the delivery of MSC 24 hours post-MI did not improve ejection fraction (EF) (p=0.19), and did not prevent the decline in EF observed in the absence of cell therapy (p=0.17). The administration of USSC also did not improve EF(p=0.11), but did prevent a further decline in EF (p=0.001). Delivery of guided USSC (cUSSC) significantly improved EF (p=0.03). Guided USSC restored function to a greater extent than MSC (p=0.03). Infarct area (p=0.2), apoptosis (p=0.07) and angiogenesis (p=0.09) did not differ between groups. Microarray analysis revealed that, following pre-implantation guiding, the gene groupings of mitosis, signalling and 
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