Guillermo García-Cardeña, PhD

A research team led by Guillermo García-Cardeña, PhD, director of the BWH Laboratory for Systems Biology at the Center for Excellence in Vascular Biology, Department of Pathology, has generated  vascular endothelium—the layer of cells that line the inner surface of blood vessels—from human-induced pluripotent stem cells (iPSCs). iPSCs are derived from adult cells in the body that are genetically manipulated to pluripotent cells with the capacity to be transformed to many cells types.

The endothelium generated by the researchers was carefully characterized and shown to exhibit rich functional plasticity similar to mature primary vascular endothelium. They respond to diverse proinflammatory stimuli, adopt an activated phenotype including adhesion molecule expression, cytokine (cell-signaling) production, and support for leukocyte (a type of white blood cell) transmigration. They also maintain dynamic barrier properties that respond to various vascular permeability factors. Moreover, when biomechanical or pharmacological stimuli are applied, the cells can induce pathophysiologically relevant atheroprotective or atheroprone phenotypes.

“Our results show that human iPSC-derived endothelium has a repertoire of functional phenotypic plasticity and is amenable to cell-based assays probing endothelial contributions to inflammatory and cardiovascular disease in a patient-specific manner,” said García-Cardeña. “This new experimental platform opens exciting possibilities for studying mechanisms of human disease, tissue engineering, and the development of extracorporeal organ-assisted devices.”

The study was published on August 6, 2013, in Stem Cell Reports.