Abstract
Cell transplantation is an attractive therapeutic avenue for injuries of the central nervous system (CNS) and neurodegenerative disorders. Transplanted cells are able to restore the cells that are lost in the injury process, including neurons, oligodendrocytes, and astrocytes. Various clinically relevant cell types and sources have been explored thus far, including induced pluripotent stem cells (iPSCs), which can be used for autologous transplantation. Despite this advantage, differentiation of iPSCs remains time consuming, which may be a limitation in urgent clinical cases. Additionally, the intermediate pluripotent state increases the risk of tumorigenicity when transplanting iPSCs. In this regard, research efforts have shifted toward the transdifferentiation of somatic cells into a variety of neural cell types, including neurons, astrocytes, and oligodendrocytes or their progenitors. This method bypasses the pluripotent stage to reduce the risk of tumorigenicity, thus reducing the induction timeline while still maintaining the patient-specific capacity of the cells. Neural cells or their progenitors can be differentiated in vitro using a number of methods, including transient expression or suppression of certain transcription and chromatin remodeling factors through gene manipulation, or miRNA and small molecule treatment. Recently, research efforts have also focused on in vivo transdifferentiation, in which endogenous cells are targeted for conversion into cell types of interest. The following chapter will focus on the general principles of direct neural lineage conversion, the methods used to derive particular cell types, and their application to injuries of the CNS.
Katarzyna Pieczonka and William Brett Mclntyre have contributed equally to this chapter.
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Abbreviations
- 6-OHDA:
-
6-hydroxydopamine
- AD:
-
Alzheimer’s disease
- BMA:
-
Ascl1, Brn2, Mytl1
- CNS:
-
Central nervous system
- CPZ:
-
Cuprizone
- CRISPRa:
-
CRISPR activation
- DCas9:
-
Dead form of Cas9
- DCX:
-
Doublecortin
- DRNPCs:
-
Directly reprogrammed neural progenitor cells
- HDAC:
-
Histone deacetylase
- FACS:
-
Fluorescent activated cell sorting
- IPSCs:
-
Induced pluripotent stem cell
- INSCs:
-
Induced neural stem cells
- miRNA:
-
Micro-RNA
- MACS:
-
Magnetic-activated cell sorting
- MBD2:
-
Methyl-CpG-binding domain protein 2
- MS:
-
Multiple sclerosis
- MSI1:
-
Musashi
- Ngn2:
-
Neurogenin-1
- NSCs:
-
Neural stem/progenitor cells
- OPC:
-
Oligodendrocyte precursor cell
- ORF:
-
Open reading frame
- PD:
-
Parkinson’s disease
- RA:
-
Retinoic acid
- SCI:
-
Spinal cord injury
- SCRNASeq:
-
Single-cell RNA sequencing
- SGRNA:
-
Single guide RNA
- SHH:
-
Sonic hedgehog
- TBI:
-
Traumatic brain injury
- TF:
-
Transcription factor
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Pieczonka, K., McIntyre, W.B., Khazaei, M., Fehlings, M.G. (2022). Direct Reprogramming Strategies for the Treatment of Nervous System Injuries and Neurodegenerative Disorders. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-19-2655-6_14
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