Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
School of Biomedicine, University of Adelaide, Adelaide, SA 5000, Australia.
Int J Mol Sci. 2022 Feb 3;23(3):1740. doi: 10.3390/ijms23031740.
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.
诱导多能干细胞(iNSCs)由体细胞重编程而来,在药物发现、疾病建模和神经疾病治疗方面具有巨大潜力。虽然研究表明,通过引入转录因子可以将人类体细胞转化为 iNSCs,但由于使用外源性基因和病毒转导载体的安全性问题,这些 iNSCs 不太可能用于临床应用。在这里,我们报告了使用小分子鸡尾酒成功地将人成纤维细胞转化为 iNSCs。此外,我们的结果表明,这些人诱导多能干细胞(hiNSCs)具有与真正的神经干细胞相似的基因表达谱,能够增殖,并能分化为神经胶质细胞和功能性神经元。这项研究共同描述了一种基于小分子的从人成纤维细胞产生 hiNSCs 的新方法,这可能对研究和治疗都有帮助。