Abstract 18108: Performing Dual Contrast Cardiac MRI to Determine the Underlying Mechanism of Cell-based Therapy

Abstract

ABSTRACT BACKGROUND: The human placenta-derived amniotic mesenchymal stem cells (hAMSCs) exhibit immunomodulatory, partially pluripotent, and precardiac properties. They express the c-kit cardiac progenitor marker and are readily reprogrammed to iPSCs (MiPSCs). Dual contrast manganese-enhanced MRI (MEMRI) and delayed enhancement MRI (DEMRI) has been developed to evaluate the cardiac restorative effects of hAMSCs, c-kit⁺ hAMSCs, and MiPSCs.

HYPOTHESIS: MEMRI and DEMRI will identify the mechanism of myocardial restoration.

METHODS: SCID-beige mice underwent LAD ligation and received 250,000 cells or normal saline (NS) in the peri-infarct region. The mice were divided into 4 arms: (1) NS (control group, n=7), (2) hAMSC (n=6), (3) c-kit⁺ hAMSC group (n=2), and (4) MiPSC group (n=3). The hAMSCs were transfected with a luciferase reporter gene. Cardiac MRI measured the scar, viable myocardium, and LVEF at weeks 1, 2, and 4. Bioluminescence imaging (BLI) was also performed and blood was drawn at week 4 to detect circulating CD34⁺ cells by flow cytometry.

RESULTS: The hAMSCs demonstrated a significant LVEF improvement compared to NS (26.0±4.7% vs. 17.5±1.9%, p<0.01) at 1 week. However, by 4 weeks, the improved LVEF was not significant. This correlated with decreasing BLI signal. On the other hand, the c-kit⁺ hAMSCs demonstrated significant LVEF improvement compared to NS after week 1 (30.2±2.1% vs. 17.5±1.9%, p<0.01) and this persisted during the study. The MiPSCs exhibited the highest LVEF in one week (31.4±1.0% vs. 17.5±1.9%, p<0.01), which was sustained for the entire 4-week duration. Additionally, MEMRI of the viable myocardium demonstrated a sustained increase after 2 weeks (86.5±3.5% vs. 74.4±3.7%, p<0.01). Remarkably, no teratoma was found.

CONCLUSIONS: The MiPSCs demonstrate the most significant functional restoration. The increased myocardial viability may suggest myocardial regeneration as the mechanism for the sustained benefit.