Therapeutic approaches based on stem cells have received considerable attention as potential treatments for Huntington's disease (HD), which is a fatal, inherited neurodegenerative disorder, caused by progressive loss of GABAergic medium spiny neurons (MSNs) in the striatum of the forebrain. Transplantation of stem cells or their derivatives in animal models of HD, efficiently improved functions by replacing the damaged or lost neurons. In particular, neural stem cells (NSCs) for HD treatments have been developed from various sources, such as the brain itself, the pluripotent stem cells (PSCs), and the somatic cells of the HD patients. However, the brain-derived NSCs are difficult to obtain, and the PSCs have to be differentiated into a population of the desired neuronal cells that may cause a risk of tumor formation after transplantation. In contrast, induced NSCs, derived from somatic cells as a new stem cell source for transplantation, are less likely to form tumors. Given that the stem cell transplantation strategy for treatment of HD, as a genetic disease, is to replace the dysfunctional or lost neurons, the correction of mutant genes containing the expanded CAG repeats is essential. In this review, we will describe the methods for obtaining the optimal NSCs for transplantation-based HD treatment and the differentiation conditions for the functional GABAergic MSNs as therapeutic cells. Also, we will discuss the valuable gene correction of the disease stem cells by the CRISPR/Cas9 system for HD treatment.
Bibliographical noteFunding Information:
This work was supported by grants from the Ministry of Science, ICT and Future Planning ( 2012M3A9C6050131 and 2017M3A9C6026996 ) and the Ministry of Health & Welfare ( HR14C0007 ) of the Government of the Republic of Korea.
© 2017 Elsevier Inc.
- Gene correction
- Huntington's disease
- Induced neural stem cells
- Stem cell-based therapies
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)