Physiological Coupling of Donor and Host Cardiomyocytes After Cellular Transplantation

TLDR

Cellular transplantation is a promising strategy for treating diseased hearts, yet it remains unclear whether functional improvements arise from direct integration of donor myocytes or from indirect effects such as enhanced revascularization or altered post‑injury remodeling. The study aimed to determine whether donor cardiomyocytes can functionally integrate with host myocardium by transplanting fetal transgenic cardiomyocytes expressing enhanced green fluorescent protein into adult mouse hearts. The authors employed two‑photon laser scanning microscopy to simultaneously image calcium transients in donor and host cardiomyocytes within intact recipient hearts. Donor cardiomyocytes exhibited calcium transients that were synchronous and kinetically indistinguishable from neighboring host cells, demonstrating functional coupling and the formation of a functional syncytium with the host myocardium.

Abstract

Cellular transplantation has emerged as a potential approach to treat diseased hearts. Although cell transplantation can affect global heart function, it is not known if this results directly via functional integration of donor myocytes or indirectly via enhanced revascularization and/or altered postinjury remodeling. To determine the degree to which donor cardiomyocytes are able to functionally integrate with the host myocardium, fetal transgenic cardiomyocytes expressing enhanced green fluorescent protein were transplanted into the hearts of nontransgenic adult mice. Two-photon molecular excitation laser scanning microscopy was then used to simultaneously image cellular calcium transients in donor and host cells within the intact recipient hearts. Calcium transients in the donor cardiomyocytes were synchronous with and had kinetics indistinguishable from those of neighboring host cardiomyocytes. These results strongly suggest that donor cardiomyocytes functionally couple with host cardiomyocytes and support the notion that transplanted cardiomyocytes can form a functional syncytium with the host myocardium.