S4: Drug Toxicity Screening using human stem cells

Drug Toxicity Screening using human stem cells

S4: Drug Toxicity Screening using human stem cells, OpenTox Asia 2017

Kyun-Sun Kang 


Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University




Human stem cells including induced pluripotent stem cells and induced adult stem cells are thought to be useful for the prediction of drug-induced toxicity and for the alternative methods substitute of animal testing. Recently, human induced neural stem cells (iNSC) from skin fibroblasts of a Niemann-Pick disease type C (NPC) patient that suffers from a neurodegenerative and lysosomal lipid storage disorders were generated. Established NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes. However, importantly, NPC-iNSCs retained the main features of NPC, displaying defects in self-renewal and neuronal differentiation accompanied by abnormal cholesterol accumulation. For the use as a drug screening platform, these NPC-iNSCs were analyzed to treat valproic acid, a well-known therapeutic molecule, and shown that impaired phenotypes were recapitulated comparable to WT-iNSCs. Moreover, graphene could restore the cholesterol accumulation and neuronal differentiation in NPC-iNSCs. Subsequently, graphene provided its therapeutic role in a NPC1-kockout mouse model. Taken together, these findings suggest that NPC-iNSCs can serve as an unlimited source of neural cells for pathological study and also drug screening in a patient specific manner.