Abstract
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.
Highlights
Mesenchymal stromal cells (MSC) represent a multipotent cell population capable to differentiate into different cell types [1]
We examined whether MSC derived from different sources, including bone marrow (BM), dental follicle and subcutaneous adipose tissue can be driven towards a cardiac lineage using a transient reprogramming strategy based on miRNA and mRNA transfection
We found that stromal (PCA) was performed to show the common clustering of the triplicates
Summary
Mesenchymal stromal cells (MSC) represent a multipotent cell population capable to differentiate into different cell types [1]. They are an -accessible cell source as they can be isolated at high yields from various kinds of human tissue, such as umbilical cord, bone marrow, dental pulp, adipose tissue, placenta, etc. The common mesenchymal cell types that emanate from MSC are osteocytes, chondrocytes, and adipocytes [2]. Due to their plasticity, MSC are considered as one of the most important cell types for the application in regenerative medicine as demonstrated by a huge number of pre-clinical studies and several clinical trials [3,4]. It is commonly accepted that the observed therapeutic impact induced by MSCs is mainly based on the secretion of paracrine factors rather than on the differentiation into cardiomyocytes
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