Abstract:
While medical practices have evolved tremendously on the immediate aftermath of a myocardial infarction (MI), there are no techniques currently administered to slow, cease, or reverse the negative side effects of an occluded artery. Previous work has demonstrated that the extent of myocardiocyte cell death and subsequent scar formation following MI can be decreased by the administration of “survival signals”, such as those secreted by mesenchymal stem cells, to the damaged myocardium. While the therapeutic effects of such factors have been documented, the difficulty lies in the ability to maintain a constant flux of secretion factors to the site of damage. We have engineered a hydrogel construct optimized to release survival signals from encapsulated stem cells directly to the myocardium to reduce the tissue degradation associated with MI’s.
Hydrogel patches composed of a combination of PEDGA and MA have been engineered to support cell viability and initiate a neovascularization response in egg membrane assays. With possible beneficial properties shown in vitro, an in vivo approach has been taken to test the efficacy and possible treatment of ischemia in the heart. We have adopted a mouse myocardial infarction model to test the efficacy of a cell encapsulated hydrogel patch on the survival of cardiac tissue following ischemia. To maintain patch adhesion to the heart surface, we have developed a biocompatible glue that ensures long term patch-to-tissue interactions. Work is currently underway to test the efficacy of encapsulated mesenchymal stem cells in aiding in tissue healing and preventing tissue degradation using a combination of cardiomyocyte co-culturing techniques, echocardiogram measurements, and histological testing.
This work was funded by US Army Grant (W81XWH-08-1-0701) and a Fellowship from Carle Foundation Hospital.
Research was also presented at the Keystone Symposia on Molecular and Cellular Biology, April 3-7, Snowbird, UT.