Media supplements for differentiation of cardiomyocytes

Abstract

One of the most important challenges in cell-based therapy for the treatment of cardiovascular diseases is to increase the cardiomyocyte (CMC) yield. Current cell-based therapies include the expansion and differentiation of adult mesenchymal stem cells or embryonic stem cells to produce functional CMCs. An approximated 2 billion cells is required for therapeutic application. A platform capable of producing such numbers was demonstrated through the use of a p38 mitogen-activated protein kinase inhibitor SB203580 and microcarriers, TSK-GEL. However, a current limitation to the platform is the culture media. The culture media used in cardiomyogenesis has yet to be refined. Many factors needed for cell growth inhibits differentiation such as serum and insulin. Because of this limiting factor, the amount of cell death during the initial stages of differentiation is extremely high. The aim of this study is to enhance CMC yield via a screening process to identify supplements (A to E) that can improve cell growth or CMC yield. Our results isolated supplements A (Conc. A) and D (Conc. B) as key inducers that were able to enhance CMC yield by about 2.3 fold increase in CMC yield. Further investigation also showed that supplement A aided TSK-GEL in achieving an optimal aggregate size. This study provides insights into the possibilities of enhancing CMC yield and producing CMCs in large numbers.