In vitro and in vivo induction of human embryonic stem cells differentiated into rosette neural stem cells and further generation of neuron-like cells

Abstract

ABSTRACT Nervous system diseases, especially degenerative diseases of the central nervous system (CNS), seriously endanger human health, and the injured adult neurons are difficult to self-renew. Therefore, cell replacement therapy with good application prospects has become a hot spot in biomedical research. Human embryonic stem cells (hESCs) are promising sources of cells with unlimited proliferation ability and multiple differentiation potential. The purpose of this study was to use these characteristics of hESCs to obtain a large number of differentiated and stable neural stem cells (NSCs) and provide potential tissue engineering materials for the treatment of neurological diseases. Cultured on low adhesion plate for 4 days in vitro, the hESCs can differentiate into suspended embryoid bodies (EBs). After further culture of EBs for 4 days, high-purity Nestin-positive NSCs with typical rosette structure can be induced, and these cells can further differentiate into a variety of mature nerve cells. Meanwhile, hESCs could form in vivo typical teratomas that contained rosette structures. Our results indicated that hESCs had the ability to differentiate into rosette NSCs both in vitro and in vivo, and the bioactive rosettes are of great significance to understanding the mechanism of neural development and studying the treatment of neurodegenerative diseases.