Induced pluripotent stem cell models from X‐linked adrenoleukodystrophy patients

Abstract

X-ALD iPSC model recapitulates the key events of disease development (ie, VLCFA accumulation in oligodendrocytes), provides new clues for better understanding of the disease, and allows for early and accurate diagnosis of the disease subtypes. X-ALD oligodendrocytes can be a useful cell model system to develop new therapeutics for treating X-ALD.

HDAC inhibitor SAHA normalizes the levels of VLCFAs in human skin fibroblasts from X-ALD patients and downregulates the expression of proinflammatory cytokines in Abcd1/2-silenced mouse astrocytes

“…Second, the effects of PBA were not long-lasting; the initially decreased VLCFA levels later returned to pretreatment levels in longterm studies ( 84 ). In a recent report, published while this manuscript was under review, a millimolar concentration of PBA was required for lowering the VLCFA levels in cultured oligodendrocytes differentiated from pluripotent stem cells of X-ALD patients ( 85 ). Furthermore, PBA/PA are nonselective inhibitors of HDAC and have been reported to inhibit the mevalonate pathway ( 86 ).…”

Bio-inspired oligovitronectin-grafted surface for enhanced self-renewal and long-term maintenance of human pluripotent stem cells under feeder-free conditions

“…hiPSCs (wild-type and childhood cerebral adrenoleukodystrophy (CCALD)-specific [29]) and hESCs (line H9) were maintained on STO-feeder layers in Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 (DMEM-F12) medium (Invitrogen, Carlsbad, CA, USA) supplemented with 20% knockout serum replacement (Invitrogen), 1% non-essential amino acids (Invitrogen), 1% Pen-Strep (Invitrogen), bmercaptoethanol (SigmaeAldrich), and 50 ng/ml of fibroblast growth factor-2 (Peprotech, Rocky Hill, NJ, USA). STO fibroblasts were inactivated by treatment with 10 mg/ml mitomycin C (SigmaeAldrich) before use.…”

Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs

“…In vitro differentiation of the iPSCs into three germ layers was induced as described (50,51). Embryoid bodies (EBs), formed by partially dissociating iPSCs using collagenase type IV (Invitrogen), were transferred to ultralow attachment plates (Corning) and cultured in DMEM/F12 (1:1) medium supplemented with 20% knockout serum (Invitrogen), 4.5 g/L L-glutamine, 1% nonessential amino acids, 0.1 mM 2-mercaptoethanol, and 5% FBS.…”