Methods of reactivation and reprogramming of neural stem cells for neural repair

Zuojun Tian, Qiuge Zhao, Sangita Biswas, Wenbin Deng

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Research on the biology of adult neural stem cells (NSCs) and induced NSCs (iNSCs), as well as NSC-based therapies for diseases in central nervous system (CNS) has started to generate the expectation that these cells may be used for treatments in CNS injuries or disorders. Recent technological progresses in both NSCs themselves and their derivatives have brought us closer to therapeutic applications. Adult neurogenesis presents in particular regions in mammal brain, known as neurogenic niches such as the dental gyrus (DG) in hippocampus and the subventricular zone (SVZ), within which adult NSCs usually stay for long periods out of the cell cycle, in G0. The reactivation of quiescent adult NSCs needs orchestrated interactions between the extrinsic stimulis from niches and the intrinsic factors involving transcription factors (TFs), signaling pathway, epigenetics, and metabolism to start an intracellular regulatory program, which promotes the quiescent NSCs exit G0 and reenter cell cycle. Extrinsic and intrinsic mechanisms that regulate adult NSCs are interconnected and feedback on one another. Since endogenous neurogenesis only happens in restricted regions and steadily fails with disease advances, interest has evolved to apply the iNSCs converted from somatic cells to treat CNS disorders, as is also promising and preferable. To overcome the limitation of viral-based reprogramming of iNSCs, bioactive small molecules (SM) have been explored to enhance the efficiency of iNSC reprogramming or even replace TFs, making the iNSCs more amenable to clinical application. Despite intense research efforts to translate the studies of adult and induced NSCs from the bench to bedside, vital troubles remain at several steps in these processes. In this review, we examine the present status, advancement, pitfalls, and potential of the two types of NSC technologies, focusing on each aspects of reactivation of quiescent adult NSC and reprogramming of iNSC from somatic cells, as well as on progresses in cell-based regenerative strategies for neural repair and criteria for successful therapeutic applications.

Original languageEnglish (US)
JournalMethods
DOIs
StateAccepted/In press - 2017

Fingerprint

Neural Stem Cells
Stem cells
Repair
Adult Stem Cells
Neurology
Central Nervous System Diseases
Neurogenesis
Cell Cycle
Transcription Factors
Cells
Nervous System Trauma
Parahippocampal Gyrus
Intrinsic Factor
Mammals
Lateral Ventricles
Cell- and Tissue-Based Therapy
Nervous System Diseases
Research
Metabolism
Epigenomics

Keywords

  • Adult neural stem cell
  • Induced neural stem cell
  • Neurogenesis
  • Reactivation
  • Reprogramming

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Methods of reactivation and reprogramming of neural stem cells for neural repair. / Tian, Zuojun; Zhao, Qiuge; Biswas, Sangita; Deng, Wenbin.

In: Methods, 2017.

Research output: Contribution to journalArticle

@article{be3112a760c844cfbe7b479401b4c3ab,
title = "Methods of reactivation and reprogramming of neural stem cells for neural repair",
abstract = "Research on the biology of adult neural stem cells (NSCs) and induced NSCs (iNSCs), as well as NSC-based therapies for diseases in central nervous system (CNS) has started to generate the expectation that these cells may be used for treatments in CNS injuries or disorders. Recent technological progresses in both NSCs themselves and their derivatives have brought us closer to therapeutic applications. Adult neurogenesis presents in particular regions in mammal brain, known as neurogenic niches such as the dental gyrus (DG) in hippocampus and the subventricular zone (SVZ), within which adult NSCs usually stay for long periods out of the cell cycle, in G0. The reactivation of quiescent adult NSCs needs orchestrated interactions between the extrinsic stimulis from niches and the intrinsic factors involving transcription factors (TFs), signaling pathway, epigenetics, and metabolism to start an intracellular regulatory program, which promotes the quiescent NSCs exit G0 and reenter cell cycle. Extrinsic and intrinsic mechanisms that regulate adult NSCs are interconnected and feedback on one another. Since endogenous neurogenesis only happens in restricted regions and steadily fails with disease advances, interest has evolved to apply the iNSCs converted from somatic cells to treat CNS disorders, as is also promising and preferable. To overcome the limitation of viral-based reprogramming of iNSCs, bioactive small molecules (SM) have been explored to enhance the efficiency of iNSC reprogramming or even replace TFs, making the iNSCs more amenable to clinical application. Despite intense research efforts to translate the studies of adult and induced NSCs from the bench to bedside, vital troubles remain at several steps in these processes. In this review, we examine the present status, advancement, pitfalls, and potential of the two types of NSC technologies, focusing on each aspects of reactivation of quiescent adult NSC and reprogramming of iNSC from somatic cells, as well as on progresses in cell-based regenerative strategies for neural repair and criteria for successful therapeutic applications.",
keywords = "Adult neural stem cell, Induced neural stem cell, Neurogenesis, Reactivation, Reprogramming",
author = "Zuojun Tian and Qiuge Zhao and Sangita Biswas and Wenbin Deng",
year = "2017",
doi = "10.1016/j.ymeth.2017.08.014",
language = "English (US)",
journal = "Methods",
issn = "0076-6879",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Methods of reactivation and reprogramming of neural stem cells for neural repair

AU - Tian, Zuojun

AU - Zhao, Qiuge

AU - Biswas, Sangita

AU - Deng, Wenbin

PY - 2017

Y1 - 2017

N2 - Research on the biology of adult neural stem cells (NSCs) and induced NSCs (iNSCs), as well as NSC-based therapies for diseases in central nervous system (CNS) has started to generate the expectation that these cells may be used for treatments in CNS injuries or disorders. Recent technological progresses in both NSCs themselves and their derivatives have brought us closer to therapeutic applications. Adult neurogenesis presents in particular regions in mammal brain, known as neurogenic niches such as the dental gyrus (DG) in hippocampus and the subventricular zone (SVZ), within which adult NSCs usually stay for long periods out of the cell cycle, in G0. The reactivation of quiescent adult NSCs needs orchestrated interactions between the extrinsic stimulis from niches and the intrinsic factors involving transcription factors (TFs), signaling pathway, epigenetics, and metabolism to start an intracellular regulatory program, which promotes the quiescent NSCs exit G0 and reenter cell cycle. Extrinsic and intrinsic mechanisms that regulate adult NSCs are interconnected and feedback on one another. Since endogenous neurogenesis only happens in restricted regions and steadily fails with disease advances, interest has evolved to apply the iNSCs converted from somatic cells to treat CNS disorders, as is also promising and preferable. To overcome the limitation of viral-based reprogramming of iNSCs, bioactive small molecules (SM) have been explored to enhance the efficiency of iNSC reprogramming or even replace TFs, making the iNSCs more amenable to clinical application. Despite intense research efforts to translate the studies of adult and induced NSCs from the bench to bedside, vital troubles remain at several steps in these processes. In this review, we examine the present status, advancement, pitfalls, and potential of the two types of NSC technologies, focusing on each aspects of reactivation of quiescent adult NSC and reprogramming of iNSC from somatic cells, as well as on progresses in cell-based regenerative strategies for neural repair and criteria for successful therapeutic applications.

AB - Research on the biology of adult neural stem cells (NSCs) and induced NSCs (iNSCs), as well as NSC-based therapies for diseases in central nervous system (CNS) has started to generate the expectation that these cells may be used for treatments in CNS injuries or disorders. Recent technological progresses in both NSCs themselves and their derivatives have brought us closer to therapeutic applications. Adult neurogenesis presents in particular regions in mammal brain, known as neurogenic niches such as the dental gyrus (DG) in hippocampus and the subventricular zone (SVZ), within which adult NSCs usually stay for long periods out of the cell cycle, in G0. The reactivation of quiescent adult NSCs needs orchestrated interactions between the extrinsic stimulis from niches and the intrinsic factors involving transcription factors (TFs), signaling pathway, epigenetics, and metabolism to start an intracellular regulatory program, which promotes the quiescent NSCs exit G0 and reenter cell cycle. Extrinsic and intrinsic mechanisms that regulate adult NSCs are interconnected and feedback on one another. Since endogenous neurogenesis only happens in restricted regions and steadily fails with disease advances, interest has evolved to apply the iNSCs converted from somatic cells to treat CNS disorders, as is also promising and preferable. To overcome the limitation of viral-based reprogramming of iNSCs, bioactive small molecules (SM) have been explored to enhance the efficiency of iNSC reprogramming or even replace TFs, making the iNSCs more amenable to clinical application. Despite intense research efforts to translate the studies of adult and induced NSCs from the bench to bedside, vital troubles remain at several steps in these processes. In this review, we examine the present status, advancement, pitfalls, and potential of the two types of NSC technologies, focusing on each aspects of reactivation of quiescent adult NSC and reprogramming of iNSC from somatic cells, as well as on progresses in cell-based regenerative strategies for neural repair and criteria for successful therapeutic applications.

KW - Adult neural stem cell

KW - Induced neural stem cell

KW - Neurogenesis

KW - Reactivation

KW - Reprogramming

UR - http://www.scopus.com/inward/record.url?scp=85028661182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028661182&partnerID=8YFLogxK

U2 - 10.1016/j.ymeth.2017.08.014

DO - 10.1016/j.ymeth.2017.08.014

M3 - Article

C2 - 28864354

AN - SCOPUS:85028661182

JO - Methods

JF - Methods

SN - 0076-6879

ER -