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Multipotent adult mesenchymal stromal cells (MSCs) could represent an elegant source for the generation of patient-specific cardiomyocytes needed for regenerative medicine, cardiovascular research, and pharmacological studies. However, the differentiation of adult MSC into a cardiac lineage is challenging compared to embryonic stem cells or induced pluripotent stem cells. Here we used non-integrative methods, including microRNA and mRNA, for cardiac reprogramming of adult MSC derived from bone marrow, dental follicle, and adipose tissue. We found that MSC derived from adipose tissue can partly be reprogrammed into the cardiac lineage by transient overexpression of GATA4, TBX5, MEF2C, and MESP1, while cells isolated from bone marrow, and dental follicle exhibit only weak reprogramming efficiency. qRT-PCR and transcriptomic analysis revealed activation of a cardiac-specific gene program and up-regulation of genes known to promote cardiac development. Although we did not observe the formation of fully mature cardiomyocytes, our data suggests that adult MSC have the capability to acquire a cardiac-like phenotype when treated with mRNA coding for transcription factors that regulate heart development. Yet, further optimization of the reprogramming process is mandatory to increase the reprogramming efficiency.

Das übergeordnete Ziel der Arbeiten war, Methoden im Mausmodell zu entwickeln und zu evaluieren, mit denen das Verhalten intramyokardial transplantierter Zellen, deren Wirkmechanismus und deren Effekt auf das linksventrikuläre Remodeling in-vivo gemessen werden kann. Das Schicksal der transplantierten Zellen und die Wirkmechanismen – zelluläre Inflammation und Angiogenese – wurden dabei vor allem mittels Positronen-Emissions-Tomographie (PET) untersucht. Für die Etablierung der Bildgebung des LV Remodeling spielte die kardiale Magnetresonanztomographie (MRT) die tragende Rolle.