In vivo reprogramming reactive glia into iPSCs to produce new neurons in the cortex following traumatic brain injury

Xiang Gao, Xiaoting Wang, Wenhui Xiong, Jinhui Chen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) results in a significant amount of cell death in the brain. Unfortunately, the adult mammalian brain possesses little regenerative potential following injury and little can be done to reverse the initial brain damage caused by trauma. Reprogramming adult cells to generate induced pluripotent stem cell (iPSCs) has opened new therapeutic opportunities to generate neurons in a non-neurogenic regions in the cortex. In this study we showed that retroviral mediated expression of four transcription factors, Oct4, Sox2, Klf4, and c-Myc, cooperatively reprogrammed reactive glial cells into iPSCs in the adult neocortex following TBI. These iPSCs further differentiated into a large number of neural stem cells, which further differentiated into neurons and glia in situ, and filled up the tissue cavity induced by TBI. The induced neurons showed a typical neuronal morphology with axon and dendrites, and exhibited action potential. Our results report an innovative technology to transform reactive glia into a large number of functional neurons in their natural environment of neocortex without embryo involvement and without the need to grow cells outside the body and then graft them back to the brain. Thus this technology offers hope for personalized regenerative cell therapies for repairing damaged brain.

Original languageEnglish (US)
Article number22490
JournalScientific Reports
Volume6
DOIs
StatePublished - Mar 9 2016

Fingerprint

Induced Pluripotent Stem Cells
Neuroglia
Neurons
Brain
Neocortex
Technology
Neural Stem Cells
Wounds and Injuries
Cell- and Tissue-Based Therapy
Dendrites
Action Potentials
Axons
Cell Death
Transcription Factors
Embryonic Structures
Traumatic Brain Injury
Transplants

ASJC Scopus subject areas

  • General

Cite this

In vivo reprogramming reactive glia into iPSCs to produce new neurons in the cortex following traumatic brain injury. / Gao, Xiang; Wang, Xiaoting; Xiong, Wenhui; Chen, Jinhui.

In: Scientific Reports, Vol. 6, 22490, 09.03.2016.

Research output: Contribution to journalArticle

@article{00f60ef19f24439aa4e36aa8ed070c9a,
title = "In vivo reprogramming reactive glia into iPSCs to produce new neurons in the cortex following traumatic brain injury",
abstract = "Traumatic brain injury (TBI) results in a significant amount of cell death in the brain. Unfortunately, the adult mammalian brain possesses little regenerative potential following injury and little can be done to reverse the initial brain damage caused by trauma. Reprogramming adult cells to generate induced pluripotent stem cell (iPSCs) has opened new therapeutic opportunities to generate neurons in a non-neurogenic regions in the cortex. In this study we showed that retroviral mediated expression of four transcription factors, Oct4, Sox2, Klf4, and c-Myc, cooperatively reprogrammed reactive glial cells into iPSCs in the adult neocortex following TBI. These iPSCs further differentiated into a large number of neural stem cells, which further differentiated into neurons and glia in situ, and filled up the tissue cavity induced by TBI. The induced neurons showed a typical neuronal morphology with axon and dendrites, and exhibited action potential. Our results report an innovative technology to transform reactive glia into a large number of functional neurons in their natural environment of neocortex without embryo involvement and without the need to grow cells outside the body and then graft them back to the brain. Thus this technology offers hope for personalized regenerative cell therapies for repairing damaged brain.",
author = "Xiang Gao and Xiaoting Wang and Wenhui Xiong and Jinhui Chen",
year = "2016",
month = "3",
day = "9",
doi = "10.1038/srep22490",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - In vivo reprogramming reactive glia into iPSCs to produce new neurons in the cortex following traumatic brain injury

AU - Gao, Xiang

AU - Wang, Xiaoting

AU - Xiong, Wenhui

AU - Chen, Jinhui

PY - 2016/3/9

Y1 - 2016/3/9

N2 - Traumatic brain injury (TBI) results in a significant amount of cell death in the brain. Unfortunately, the adult mammalian brain possesses little regenerative potential following injury and little can be done to reverse the initial brain damage caused by trauma. Reprogramming adult cells to generate induced pluripotent stem cell (iPSCs) has opened new therapeutic opportunities to generate neurons in a non-neurogenic regions in the cortex. In this study we showed that retroviral mediated expression of four transcription factors, Oct4, Sox2, Klf4, and c-Myc, cooperatively reprogrammed reactive glial cells into iPSCs in the adult neocortex following TBI. These iPSCs further differentiated into a large number of neural stem cells, which further differentiated into neurons and glia in situ, and filled up the tissue cavity induced by TBI. The induced neurons showed a typical neuronal morphology with axon and dendrites, and exhibited action potential. Our results report an innovative technology to transform reactive glia into a large number of functional neurons in their natural environment of neocortex without embryo involvement and without the need to grow cells outside the body and then graft them back to the brain. Thus this technology offers hope for personalized regenerative cell therapies for repairing damaged brain.

AB - Traumatic brain injury (TBI) results in a significant amount of cell death in the brain. Unfortunately, the adult mammalian brain possesses little regenerative potential following injury and little can be done to reverse the initial brain damage caused by trauma. Reprogramming adult cells to generate induced pluripotent stem cell (iPSCs) has opened new therapeutic opportunities to generate neurons in a non-neurogenic regions in the cortex. In this study we showed that retroviral mediated expression of four transcription factors, Oct4, Sox2, Klf4, and c-Myc, cooperatively reprogrammed reactive glial cells into iPSCs in the adult neocortex following TBI. These iPSCs further differentiated into a large number of neural stem cells, which further differentiated into neurons and glia in situ, and filled up the tissue cavity induced by TBI. The induced neurons showed a typical neuronal morphology with axon and dendrites, and exhibited action potential. Our results report an innovative technology to transform reactive glia into a large number of functional neurons in their natural environment of neocortex without embryo involvement and without the need to grow cells outside the body and then graft them back to the brain. Thus this technology offers hope for personalized regenerative cell therapies for repairing damaged brain.

UR - http://www.scopus.com/inward/record.url?scp=84960503462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960503462&partnerID=8YFLogxK

U2 - 10.1038/srep22490

DO - 10.1038/srep22490

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 22490

ER -