Human adult somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells upon the introduction of four transcription factors that are part of the pluripotency network in embryonic stem cells. The ability to readily from patients with disease has ushered in new opportunities to understand disease mechanisms, screen for therapeutics, and consider regenerative approaches using personalized human cells. In this session, several examples of the use of iPS cells in novel ways were presented.

By making iPS cells from patients with genetically defined disease, the investigators were able to differentiate the pluripotent cells into the cell type affected by the congenital cardiovascular disorder. These cells carried the disease-causing mutation and provided a platform for understanding the cellular and molecular consequences of the mutation in the most relevant human cells. Deep interrogation of such cells promises to reveal fundamental mechanisms of disease and should point to new targets to intervene in the disease process. This is being done for diseases involving cardiomyocytes, smooth muscle cells, and endothelial cells, each of which can be easily differentiated from human iPS cells with good efficiency and purity. Once new targets for disease pathology are discovered in such cells, small molecule or biologic screens can be performed to identify lead candidates for new therapeutics. For those congenital diseases that have ongoing consequences after birth, there is potential to intervene postnatally in the disease evolution.

In addition to the use of iPS cells for disease modeling and drug discovery, there are robust efforts to use pluripotent stem cells for regenerative medicine. Such efforts often involve bioengineering approaches to assemble stem cell-derived cardiomyocytes into a three-dimensional structure. This can be useful for cardiomyocytes, valves, or vessels. The use of iPS cells may allow personalized tissues to be developed, as tissue could be generated with one’s own cells. New approaches using efficient gene-editing techniques may allow correction of abnormal genes and subsequent use of corrected cells for transplant. Other types of progenitor cells are also being studied for their regenerative capacity and are discussed in this section.

While there is great hope that the use of iPS cells will lead to new therapeutic approaches, many hurdles must be overcome. For disease modeling, purifying specific subtypes of cells that are affected by disease will be important, as will the ability to generate more mature, adult-like cells from the iPS cells. For regenerative medicine approaches, the ability to generate mature cells that can survive and integrate upon transplantation will be critical and will likely require clever engineering strategies. Nevertheless, it is likely that iPS-based technologies will provide us a better understanding of human disease and lead to new interventions.