Making cardiomyocytes with your chemistry set: Small molecule-induced cardiogenesis in somatic cells

Abstract

Cell transplantation is an attractive potential therapy for heart diseases. For example, myocardial infarction (MI) is a leading cause of mortality in many countries. Numerous medical interventions have been developed to stabilize patients with MI and, although this has increased survival rates, there is currently no clinically approved method to reverse the loss of cardiac muscle cells (cardiomyocytes) that accompanies this disease. Cell transplantation has been proposed as a method to replace cardiomyocytes, but a safe and reliable source of cardiogenic cells is required. An ideal source would be the patients' own somatic tissue cells, which could be converted into cardiogenic cells and transplanted into the site of MI. However, these are difficult to produce in large quantities and standardized protocols to produce cardiac cells would be advantageous for the research community. To achieve these research goals, small molecules represent attractive tools to control cell behavior. In this editorial, we introduce the use of small molecules in stem cell research and summarize their application to the induction of cardiogenesis in non-cardiac cells. Exciting new developments in this field are discussed, which we hope will encourage cardiac stem cell biologists to further consider employing small molecules in their culture protocols.

Keywords: Cardiogenesis; Cardiovascular disease; Cell reprogramming; Small molecules; Somatic cells.

Figure 1

Selected small molecules that are used to regulate cardiogenesis (in alphabetical order). BMP: Bone morphogenetic; MAPK: Mitogen-activated protein kinase; TGF-β: Transforming growth factor-β.

Figure 2

Pathways of small molecule-mediated cardiomyocyte production. It is now established that cardiomyocyte differentiation can be induced in multiple cells types using small molecule-based approaches. Embryonic stem cells and induced pluripotent stem cells are typically induced to undergo cardiac mesoderm differentiation before culture conditions are switched to cardiomyocyte differentiation media. “Partially” induced stem cells are somatic cells that were transfected with induced pluripotent stem cells reprogramming factors and then treated with the small molecule, JAK inhibitor-1 (as described in the text).