Human Cardiomyocyte Biology
In 2007 Shinya Yamanaka rebooted the world of cardiac research by identifying a way to reprogram human cells into a naive, pluripotent state (induced pluripotent ste cells, iPSC) from which any cell lineage could be derived. This opened up avenues do interrogate human heart cells “cardiomyocytes” in new and exciting ways with unprecedented resolution. Cardiomyocytes generated from iPSC are refered to as iPSC-CMs. We use iPSC-CMs to 1) answer specific cell biological questions 2) to understand mechanisms of congenital cardiomyopathies, 3) develop novel small molecules to modulate cardiac cell fates and functions and 4) develop technologies to mature, and assess iPSC-CM structure and function.
Through highly effecient and reproducible, small molecule mediated cardiomyocyte induction protocols it is possible to get populations of cardiomyocytes that are 98% pure. These spontaneously beating sheets (seen above) can be analyzed with indicator dies such as Fluo4 to visualize calcium levels or through motion analysis. These bulk cardiomyocyte methods are useful for studying rates of contractility governed by channels and are responsible for arrythmia. However, these bulk methods are not good for assessing contractile strength or quantifying the degree of a cardiomyocyte shortening. Hong lab alumni, addressed this shortcoming by developing the matrigel mattress, a method for the generation of single contracting human-iPSC-CMs, and the quantification of single shortening cardiomyocytes for the first time (seen below). Furthermore, we are generating new and novel mor stable mattresses for long term culture.