Generation of induced pluripotent stem cells (iPSCs) from other somatic cells has provided great hopes for transplantation therapies. However, these cells still cannot be used for clinical application due to the low reprogramming and differentiation efficiency beside the risk of mutagenesis and tumor formation. Compared to iPSCs, induced neural stem cells (iNSCs) are easier to terminally differentiate into neural cells and safe; thus, iNSCs hold more opportunities than iPSCs to treat neural diseases. On the other hand, recent studies have showed that small molecules (SMs) can dramatically improve the efficiency of reprogramming and SMs alone can even convert one kind of somatic cells into another, which is much safer and more effective than transcription factor-based methods. In this study, we provide a review of SMs that are generally used in recent neural stem cell induction studies, and discuss the main mechanisms and pathways of each SM.

No abstract

Neurological disorders are big public health challenges that are afflicting hundreds of millions of people around the world. Although many conventional pharmacological therapies have been tested in patients, their therapeutic efficacies to alleviate their symptoms and slow down the course of the diseases are usually limited. Cell therapy has attracted the interest of many researchers in the last several decades and has brought new hope for treating neurological disorders. Moreover, numerous studies have shown promising results. However, none of the studies has led to a promising therapy for patients with neurological disorders, despite the ongoing and completed clinical trials. There are many factors that may affect the outcome of cell therapy for neurological disorders due to the complexity of the nervous system, especially cell types for transplantation and the specific disease for treatment. This paper provides a review of the various cell types from humans that may be clinically used for neurological disorders, based on their characteristics and current progress in related studies.

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.