Technologies

Summary

This technology is an optimized protocol to efficiently generate cardiomyocytes from human induced pluripotent stem cells (hiPSCs).

Unmet Need: Scalable cardiomyocyte production for pharmaceutical drug screens

Given the prevalence of cardiac diseases, there is substantial demand for new therapeutics and improved methods for screening drug toxicity. Generating cardiomyocytes from hiPSCs offers a unique opportunity to study cardiac disease. While protocols have been developed that improve differentiation efficiency, these often require the use of costly and unstable recombinant proteins, which has limited large-scale production of hiPSC-derived cardiomyocytes.

The Technology: Optimized protocols for low cost, efficient differentiation of hiPSCs into cardiomyocytes

This technology describes both serum-containing and serum-free protocols for generating human cardiomyocytes from healthy control or patient-derived iPSCs. The use of cheap, defined chemicals at a low dose eliminates the need for costly recombinant factors to produce human cardiomyocytes. Analysis of in vitro cultures demonstrates that this serum-free protocol offers higher yield than current methods. Further, this technology includes dual optical fluorescent reporters, administered through lentiviral infection, that record calcium and voltage simultaneously. This allows the cardiomyocytes to be characterized and monitored during extended time-course experiments, as well as during repeat experiments using the same cells. Taken together, the cost-effectiveness and absence of animal-derived products make this technology an important advance in generating human cardiomyocytes from iPSCs for use in screens for therapeutics and drug toxicity.

This technology has been used to generate cardiomyocytes from both control and patient-derived stem cells, with retention of the diseased phenotype.

Publications

• Song L, Awari D, Han E, Uche-Anya E, Park S, Yabe Y, Chung W, Yazawa M. “Dual optical recordings for action potentials and calcium handling in induced pluripotent stem cell models of cardiac arrhythmias using genetically encoded fluorescent indicators” Stem Cells Transl Med. 2015 May; 4(5): 468-475.