Cardiomyocytes Derived from Human Pluripotent Cells Function as Pacemakers in Rodent Model

A team of Canadian heart disease researchers has converted human pluripotent stem cells into fully functional heart pacemaker cells and demonstrated their performance in a rodent model.

The sinoatrial node (SAN), which is located in the myocardial wall near where the sinus venarum joins the right atrium, is the primary pacemaker of the heart and controls heart rate throughout life. Failure of SAN function due to congenital disease or aging results in slowing of the heart rate and inefficient blood circulation, a condition treated by implantation of an electronic pacemaker. The ability to produce pacemaker cells in vitro could lead to an alternative, biological pacemaker therapy in which the failing SAN is replaced through cell transplantation.

In working towards this goal, investigators at the McEwen Centre for Regenerative Medicine (Toronto, Canada) devised a three-week long protocol using specific growth factors to coax stem cells into differentiating into pacemaker cells (NKX2-5 cardiomyocytes).

The differentiated pacemaker cells expressed markers of the SAN lineage and displayed typical pacemaker action potentials, ion current profiles, and chronotropic responses. The investigators reported in the December 12, 2016, online edition of the journal Nature Biotechnology that when transplanted into the apex of rat hearts, the NKX2-5 cardiomyocytes were able to pace the host tissue, demonstrating their capacity to function as a biological pacemaker.

"What we are doing is human biology in a petri dish," said senior author Dr. Gordon Keller, director of the McEwen Centre for Regenerative Medicine, the senior author, and professor of medical biophysics at the University of Toronto (Canada). "We are replicating nature's way of making the pacemaker cell.

We understand the importance of precision in developmental biology in setting out the process by which organisms grow and develop. We use that same precision in the petri dish because we are replicating these same processes."

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McEwen Centre for Regenerative Medicine
University of Toronto