Abstract 18627: Cellular Encapsulation of Mesenchymal Stem Cells Enhances Cardiac Repair in a Rat Model of Myocardial Infarction
Stem cell therapies for myocardial repair have shown promise in preclinical trials, but lower than expected retention and viability of transplanted cells. In an effort to improve this, we employed an alginate encapsulation strategy for human mesenchymal stem cells (hMSCs) and attached them to the heart with a biocompatible PEG hydrogel patch in a rat MI model. Encapsulation allows for diffusion of pro-angiogenic cytokines and growth factors made by the hMSCs while maintaining them at the site of implantation. Animals were treated as follows: (1) MI only, (2) MI + gel, (3) MI + gel + empty capsules, (4) MI + gel + 1x106 non-encapsulated hMSCs or (5) MI + gel + 1x106 hMSCs encapsulated in alginate. Cells were tracked using bioluminescence (BLI) and cardiac function measured by echo and CMR. Animals treated with encapsulated hMSCs in the patch had a large increase in microvascular density in the peri-infarct area (828 ± 56 vessels/mm2; n = 6; p < 0.01) compared to other groups (MI: 121 ± 10, MI + gel: 153 ± 26, MI + gel + MSC: 198 ± 18, MI + gel + empty capsules: 215 ± 55; n = 6-9). Scar size at 28 days was also significantly reduced in encapsulated hMSC treated animals (7 ± 1 %; n = 6; p < 0.05) compared to control hearts (MI: 12 ± 1 %, MI + gel: 14 ± 2%, MI + gel + MSC: 14 ± 1%, MI + gel + empty capsules: 12 ± 2%; n = 4-8). Longitudinal BLI showed greatest hMSC retention when the cells were encapsulated. Post MI cardiac fractional shortening and ejection fraction, as measured by echo and CMR, were improved in encapsulated hMSC treated hearts (Table 1). Alginate encapsulated hMSCs attached to the heart with a hydrogel patch resulted in a highly significant improvement in left ventricular function after acute myocardial infarction. The mechanism for this markedly enhanced effect appears to be increased cell survival and retention, resulting in improved vascularization of the peri-infarct area. Cellular encapsulation may represent a new translatable strategy applicable to many cell types for regenerative therapy for CVD.
- © 2012 by American Heart Association, Inc.