Abstract 13974: The Use of Allogeneic Mesenchymal Stromal Cells to Refine the Emerging “Cell-Sheet” Technique for the Treatment of Heart Failure
We have reported that epicardial placement of cell-sheets composed of bone marrow mesenchymal stromal cells (MSCs) markedly increases donor MSC survival and amplifies paracrine effects, thereby augmenting therapeutic benefits, compared to the current cell-delivery method. It is also suggested that allogeneic MSCs may be useful for cell therapy without immunosuppression. We thus examined immune rejection and therapeutic effects of allogeneic MSC-sheets for heart failure.
Methods & Results: Flow cytometory and qRT-PCR showed that expression of MHC class I and II in rat MSCs was lesser than that of unfractionated bone marrow cells. Four weeks after coronary artery ligation, female Lewis rats underwent placement of sheets composed of 4 million MSCs from male Lewis rats (Auto group) or Fisher rats (Allo group) generated using temperature responsive dishes, or sham treatment (Cont group). Up to day 3 post treatment, Allo MSCs survived similarly to the Auto MSCs (Table), leading to analogous myocardial upregulation of HIF1α, bFGF, IGF1, SDF1, TIMP1, MMP2. However, MSC survival was more extensively reduced by day 28 in the Allo group compared to the Auto group. This corresponded with a slight increase in CD68+ and CD4+ cell accumulation within the sheet (assessed by immunolabeling) and mild myocardial upregulation of IFNγ, MCP1, IL2Ra, TNFα, and IL1β at day 3 in the Allo group (1.1-1.4 fold over the Auto group; by qRT-PCR). This immunological response was, however, eliminated by day 28. Of note, the Allo group showed enhanced cardiac function at day 28, associated with reduced fibrosis and improved neovascularization, to the same degree as the Auto group.
Conclusion: Allogeneic MSC-sheet therapy achieved sufficient early-phase donor cell survival to induce therapeutic effects equivalent to the syngeneic MSC-sheet, despite mild-moderate immunological response. This suggests that allogeneic MSCs are the preferred donor cell type for MSC-sheet therapy for heart failure.
- © 2013 by American Heart Association, Inc.