Derivation and functional analysis of patient-specific induced pluripotent stem cells as an in vitro model of chronic granulomatous disease.

摘要: Chronic granulomatous disease (CGD) is an inherited disorder of phagocytes in which NADPH oxidase defective generating reactive oxygen species. In this study, we reprogrammed three normal unrelated patient's fibroblasts (p47phox and gp91phox) to pluripotency by lentiviral transduction with defined factors. These induced pluripotent stem cells (iPSC) share the morphological features human embryonic cells, express key factors, possess high telomerase activity. Furthermore, all iPSC lines formed embryoid bodies vitro containing originating from germ layers were capable teratoma formation vivo. They isogenic original patient fibroblasts, exhibited karyotype, retained p47phox or gp91phox mutations found fibroblasts. We further demonstrated that these could be differentiated into monocytes macrophages a similar cytokine profile blood-derived under resting conditions. Most importantly, CGD-patient-specific iPSC-derived showed phagocytic properties but lacked species production, correlates clinical diagnosis CGD patients. Together results suggest represent important tool for modeling phenotypes, screening candidate drugs, development gene therapy. Stem Cells 2012; 30:599–611