This month’s featured article is from the labs of Robert Schwartz and Bradley McConnell of the University of Houston in Houston, Texas. The article was published 19 August 2016 in the journal Scientific Reports.
This study investigates early embryonic stem cells expressing Mesp1. These cells give rise to cardiac progenitor cells (CPCs), and CPCs hold great potential as therapeutic agents for the treatment of heart failure. Heart failure is marked by the loss of cardiac myocytes, and since these cells lack regenerative abilities, the heart itself cannot recover. Cell-based therapies might someday lend the heart the regenerative capacity it needs, thus there is a large need to more fully understand CPCs.
The authors specifically focused on genetic tracing of CPCs that express Mesp1. In an embryonic stem cell culture, Mesp1(+) cells were enriched for cardiac-related genes, and the authors determined the entire gene expression profile of Mesp1(+) cells using Phalanx Biotech’s Mouse OneArray Whole Genome Microarray. They compared the gene expression profile of Mesp1(+) cells to Mesp1(-) cells in the same culture. This analysis revealed nearly 800 genes uniquely enriched in Mesp1(+) cells. Interestingly, Gene Ontology categories over-represented in those genes were related to heart and blood vessel development (see image above).
The microarray results further indicated the ‘stemness’ of these progenitor cells. For example, Mesp1(+) CPCs lacked expression of pluripotent stem cell markers, which is consistent with their differentiated status. Mesp1(+) CPCs were enriched for established markers of the cardiac mesoderm, which points to an early commitment to the cardiac lineage. However, they also lowly expressed genes marking an irreversible commitment to the cardiovascular lineage, suggesting Mesp(+) CPCs are not completely differentiated.
Perhaps the most exciting results of this study were the in vivo findings from injecting Mesp1(+) CPCs into hearts that had experienced a myocardial infarction. Functional metrics showed that injecting Mesp1(+) CPCs into the infarcted myocardium improved the survivability of the animals over the course of the study (compared to untreated infarcted myocardium). The authors also looked at the type of cells that developed from the injected Mesp1(+) CPCs. Overall, the transplanted cells directly differentiated into cardiac myocytes, smooth muscle cells, and endothelial cells, and contributed to new vessel formation in the post-infarcted hearts.
In summary, the authors characterized the Mesp1(+) CPC system, which represents an exciting new platform and resource to study (1) the differentiation of cardiovascular cells, and (2) their therapeutic potential in treating injured hearts.
Liu Y et al. Mesp1 marked cardiac progenitor cells repair infarcted mouse hearts (2016). Sci Rep 6:31457.