An improved method to produce heart muscle from embryonic stem cells or induced pluripotent stem cells could potentially fulfill the demand for heart disease treatments and models of testing new heart drugs. The challenging part of making heart muscle in the laboratory is the production of cells that are all the same. Otherwise their response to drugs or their transplantation into a damaged heart will be unpredictable and unreliable. Fortunately a new study published in the journal STEM CELLS Translational Medicine may provide a way to make large, homogeneous batches of heart muscle cells.
By mixing some small molecules and growth factors together, an international research team led by investigators at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai developed a two-step system that induced embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to efficiently differentiate into ventricular heart muscle cells. This protocol was not only highly efficient but also very reproducible. It also seemed to nicely recapitulate the developmental steps of normal heart development.
“These chemically induced, ventricular-like cardiomyocytes (termed ciVCMs) exhibited the expected cardiac electrophysiological and calcium handling properties as well as the appropriate heart rate responses,” said lead investigator Ioannis Karakikes, Ph.D., of the Stanford University School Of Medicine, Cardiovascular Institute. Other members of this research team consisted of scientists from the Icahn School of Medicine at Mount Sinai, New York, and the Stem Cell & Regenerative Medicine Consortium at the University of Hong Kong.
One of the unusual aspects of this research project was the integrated approach it took. This research group combined computational and experimental systems and by using these techniques, they showed that the use of particular small molecules modulated the Wnt pathway. Signals from the Wnt pathway pass from cell to cell and play a key role in determining whether cells differentiate into an atrial or ventricular muscle cell.
“The further clarification of the molecular mechanism(s) that underlie this kind of subtype specification is essential to improving our understanding of cardiovascular development. We may be able to regulate the commitment, proliferation and differentiation of pluripotent stem cells into heart muscle cells and then harness them for therapeutic purposes,” Dr. Karakikes said.
“Most cases of heart failure are related to a deficiency of heart muscle cells in the lower chambers of the heart,” said Anthony Atala, MD, editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “An efficient, cost-effective and reproducible system for generating ventricular cardiomyocytes would be a valuable resource for cell therapies as well as drug screening.”