Our laboratory is focused on two aspects of stem cell mediated cardiac repair:
- Develop in vivo imaging methods to track the fate (survival, proliferation and differentiation) of stem cells and evaluate their effects on global and regional cardiac function. We have developed magnetic resonance imaging (MRI) methods to measure the global and contractile function in living mice.
- Examine embryonic stem cell (ESC) derived cardiomyocytes (CM) for the treatment of an infarcted heart. Utilizing murine ESCs, carrying an early cardiac specific gene whose expression is linked to an antibiotic resistant gene, we are able to purify the CM population from beating embryoid bodies and obtain sufficient number of cells for in vivo study.
The long-term goal of this project is to facilitate the clinical translation of stem cell mediated therapy for myocardial infarction by identifying the optimal cell type (ESCs, skeletal myoblasts, bone marrow derived or resident cardiac progenitor cells) and understanding the mechanism of their capability to improve the cardiac function.
The long (LA) and short (SA) axis view of a rat heart receiving 5 million ESCs, that are stably transfected with a reporter gene (HSV1-sr39tk) and labeled with SPIO particles. [F-18]FHBG signal from grafted cells are in color while myocardial wall is delineated by [N-13] ammonia signal in grey scale. Hypointense region on MR images early after injection represent distribution of cells in the myocardium (a). Over time, the hypointense area reduces while contrast-to-noise ratio remains (b) reflecting the fact that SPIO labels are diluted due to proliferation of ESCs and labels in the dead cells are transferred to macrophages as demonstrated by double staining of SPIO (c) and CD68 (d). The overlay of the two suggests that the majority of SPIO positive cells are infiltrated macrophages.
Short axis cardiac MR images of an infarcted heart 14 days after receiving 5M double-labeled ESCs (a, panel 1-4 from base to the apex of the heart). b: [F-18]FHBG images acquired from the same animal. These images have been reformatted to the short axis views as MR images. c: Co-registered PET and MR images using a mutual-information based algorithm. Color scale was used for PET signal while grey scale for MR images.