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Inducing iPSC-derived heart cells to proliferate


Inducing iPSC-derived heart cells to proliferate

Richard Mills, Enzo Porrello and James Hudson from the CCVB Laboratory for Cardiac Regeneration (SBMS, UQ) and colleagues from the CCVB Cooper-White Group (AIBN, UQ) and the Wolvetang research group (AIBN, UQ), have just published their research inducing human iPSC-derived cardiomyocyte proliferation. The findings were published in Scientific Reports in April 2016.



Inducing cardiomyocyte proliferation in post-mitotic adult heart tissue is attracting significant attention as a therapeutic strategy to regenerate the heart after injury. Model animal screens have identified several candidate signalling pathways, however, it remains unclear as to what extent these pathways can be exploited, either individually or in combination, in the human system. The advent of human cardiac cells from directed differentiation of human pluripotent stem cells (hPSCs) now provides the ability to interrogate human cardiac biology in vitro, but it remains difficult with existing culture formats to simply and rapidly elucidate signalling pathway penetrance and interplay. To facilitate high-throughput combinatorial screening of candidate biologicals or factors driving relevant molecular pathways, we developed a high-density microbioreactor array (HDMA)--a microfluidic cell culture array containing 8100 culture chambers. We used HDMAs to combinatorially screen Wnt, Hedgehog, IGF and FGF pathway agonists. The Wnt activator CHIR99021 was identified as the most potent molecular inducer of human cardiomyocyte proliferation, inducing cell cycle activity marked by Ki67, and an increase in cardiomyocyte numbers compared to controls. The combination of human cardiomyocytes with the HDMA provides a versatile and rapid tool for stratifying combinations of factors for heart regeneration.

Titmarsh D, Glass N, Mills R, Hidalgo A, Wolvetang E, Porrello E, Hudson J, Cooper-White J. Induction of Human iPSC-Derived Cardiomyocyte Proliferation Revealed by Combinatorial Screening in High Density Microbioreactor Arrays. Scientific Reports 2016, 6:24637.


You can read the full article here