Abstract 13934: Scaffold Free “Cell Sheets” Composed of Mesenchymal Stromal Cells for the Treatment of Chronic Heart Failure; In Vivo Proof-of-Concept Study
Transplantation of bone marrow mesenchymal stromal cells (MSCs) is a promising treatment for heart failure mainly due to their secretion of beneficial factors to repair the damaged myocardium. We have reported that epicardial placement of scaffold free MSC sheets generated using temperature-responsive dishes increases donor MSC survival and augments therapeutic effects for acute myocardial infarction (MI), compared to the current cell-delivery method. We now aim to expand this knowledge for establishing pre-clinical evidence of the efficacy of MSC sheet therapy for post-MI chronic heart failure which is a more feasible target of this approach.
Methods & Results: Four weeks after coronary artery ligation, female Lewis rats were transplanted with 4 million MSCs from male Lewis rats by either epicardial placement of a cell sheet (CS group) or intramyocardial injection (IM group). Sham treatment was studied as control (Cont group). Donor cell survival was markedly (>9-fold) increased at both day 3 and day 28 in the CS group compared to the IM group (Table). This corresponded with amplified myocardial upregulation of key paracrine mediators, including HIF-1α, IGF-1, SDF-1, MMP-2, TIMP-2 and VCAM-1 in the CS group compared to other two groups. The majority of donor MSCs in the CS group remained at the epicardial surface with early formation of vascular networks with the host myocardium. At day 28, the CS group achieved the most improved cardiac function among all groups studied, associated with increased neovascular formation and reduced fibrosis. Donor MSC differentiation to cardiomyocytes or mesenchymal cells was not observed in either group.
Conclusion: MSC sheet therapy provides augmented therapeutic effects for post-MI chronic heart failure through increased donor cell survival and amplified paracrine effects, compared to the current method. This poof of concept encourages us to progress this innovative approach towards clinical application for heart failure.
- © 2013 by American Heart Association, Inc.