The increasing life expectancy of the world population requires more effective treatments for neurodegenerative diseases, which are common in the elderly, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) [ref. 1]. Neural stem cells (NSCs) are essential for the development and maintenance of the function of the nervous system and have a broad therapeutic role in neurodegenerative diseases.
Neural stem cells
NSCs are cells that can self-renew and have the potential to differentiate into neurons, astrocytes, and oligodendrocytes [ref. 2]. The properties of neural stem cells are summarized as follows: (i) Generation of neural tissue [ref. 3]. (ii) Self-renewal capacity. (iii) Multipotential differentiation. (iv) Low immunogenicity. The discovery of neural stem cells shattered the conventional notion that “neurons do not regenerate” [ref. 4].
Principles of neural stem cell transplantation
The damage and death of neurons and glial cells after CNS injury or degeneration leads to the corresponding clinical symptoms. It is difficult to perform effective neuronal and glial cell repair due to the limited number of neural stem cells and the impermissible microenvironment in the brain, so stem cell transplantation therapy has a promising future in this regard [ref. 5].
Neural stem cell differentiation
To obtain scalable and well-characterized subpopulations of NSCs from pluripotent stem cells, such as human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs), different NSC differentiation protocols have been developed [ref. 6]. The commonly used protocol is based on the generation of embryoid bodies (EBs) that adhere and expand in serum-free medium containing growth factors, such as fibroblast growth factor (FGF), epidermal growth factor (EGF), neurotrophic factors (NTF) ,etc. This not only stimulates the differentiation of NSCs into linear cell populations, but also reduces cell death in host endogenous neurons, promotes their axonal/dendritic connections, and enhances the survival and engraftment of transplanted NSCs [ref. 7].
Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009;27(3):275-280.
De Gioia R, Biella F, Citterio G, et al. Neural stem cell transplantation for neurodegenerative diseases. Int J Mol Sci. 2020;21(9):3103.