Generation and characterization of disease-specific induced pluripotent stem cells

Abstract

Numerous studies have reported a recent breakthrough in iPSC technology by providing an opportunity to produce disease-specific iPSCs and accessing disease-specific iPSC-derived target cells that are used to investigate new mechanisms and new drugs. In this study, iPSCs were generated from fibroblasts of patients with incurable diseases, such as Alzheimer''s disease (AD), childhood cerebral adrenoleukodystrophy (CCALD), juvenile-onset, type I diabetes mellitus (JDM) and characterized by unique features associated with pluripotency, encompassing morphological, molecular, and functional attributes. In particular, CCALD-iPSCs were induced to differentiate into oligodendrocytes, which are the cell type affected in the CCALD brain. As a manifestation of CCALD, a high accumulation of very long chain fatty acid (VLCFA) was observed in the CCALD-iPSC-derived oligodendrocytes. Moreover, VLCFAs were reduced when treated with lovastatin by upregulation of the ABCD2 gene followed by treatment with lovastatin in those cells. Oligodendrocytes derived from CCALD-iPSCs reflected the disease phenotype and responded to a known compound. These oligodendrocytes could make a remarkable contribution in developing safe and effective medicine and understanding the etiopathophysiology of CCALD. Likewise, AD-iPSCs and JDM-iPSCs may also offer key opportunities in developing new disease models.