Conversion of Human Fibroblasts into Induced Neural Stem Cells by Small Molecules

Abstract

Induced neural stem cells (iNSCs) reprogrammed from somatic cells hold great potentials for drug discovery, disease modelling and the treatment of neurological diseases. Although studies have shown that human somatic cells can be converted into iNSCs by introducing transcription factors, these iNSCs are unlikely to be used for clinical application due to the safety concern of using exogenous genes and viral transduction vectors. Here, we report the successful conversion of human fibroblasts into iNSCs using a cocktail of small molecules. Furthermore, our results demonstrate that these human iNSCs (hiNSCs) have similar gene expression profiles to bona fide NSCs, can proliferate, and are capable of differentiating into glial cells and functional neurons. This study collectively describes a novel approach based on small molecules to produce hiNSCs from human fibroblasts, which may be useful for both research and therapeutic purposes.

Strategies for modeling aging and age-related diseases

“…However, iNSCs generated by these methods can pose safety concerns for clinical application due to the ectopic expression of genes and viral vectors. Recent reports 147 suggest a safer way of reprogramming by employing small molecules like Bix01294, RG108, CHIR99021, Ascorbic acid, Repsox, LDN193189, Y27632, and Q-VD-OPh. iNSCs thus generated expressed neural markers like SOX2, PAX6, Nestin, Olig2, L1cam, MAPT, CNTN1, MAP2, and NeuN.…”