Abstract 9611: Enhancing the “Paracrine Effects” of Mesenchymal Stem Cells to Recover Damaged Myocardium by the Use of Cell-Sheets
Recent research has shown that transplantation of mesenchymal stem cells (MSCs) recovers failing hearts mainly via paracrine effects and has prompted clinical trials of intramyocardial injection of MSC suspensions. However, this method is associated with trypsinisation-induced MSC damage and injection-related injury/inflammation of host myocardium. It is now possible to generate “cell-sheets” by means of temperature-responsive culture dishes without using disruptive reagents. Epicardial placement of MSC-sheets will be able to deliver MSCs with higher viability and functionality whilst obviating damage to the host myocardium. This will enhance the paracrine effects, by improving both MSC secretion and host myocardium response, leading to amplified therapeutic effects.
Methods & Results: After coronary artery ligation in female rats, 4 million bone marrow derived MSCs from syngeneic male rats were grafted by either intramyocardial injection (IM) or cell-sheet placement (CS). Sham treated rats served as control (Cont). Donor MSC survival was markedly increased in CS compared to IM. The majority of MSCs in CS remained at the epicardial surface, avoiding myocardial accumulation of inflammatory cells. Shortly after sheet placement, the epicardium degenerated, allowing permeation of MSC-secreted mediators into the myocardium. Differentiation of donor MSCs to cardiac or mesenchymal lineages was not observed. IM showed upregulation of HIF1α, bFGF, IL10, VCAM1, MMP2, TIMP1, IGF1, SDF1, which was associated with favorable modulations in host cardiac tissues. Of note, these molecular and cellular changes were significantly amplified in CS, in correlation to further enhanced cardiac function.
Conclusion: The cell-sheet technique improved donor MSC engraftment whilst preserving the host myocardium, resulting in augmentation of MSC-derived paracrine effects, compared to the current method. These data encourage clinical application of this approach.
- © 2011 by American Heart Association, Inc.