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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·2016·Scientific Reports
DOI 10.1038/srep22490PMC PMC4783661
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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.

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  • There are a few instances in which transient reprogramming is beneficial also during the process of tissue repair (and not only prior to the injury), as in traumatic brain injury and skin wound healing.

    “There are a few instances in which transient reprogramming is beneficial also during the process of tissue repair (and not only prior to the injury). This is the case for traumatic brain injury 221 and skin wound healing 222 .”

    From Hallmarks of aging: An expanding universe (2023) · cites this paper as [221]

    The Materials and Methods report that the reprogramming virus was injected three days after traumatic brain injury, and the Discussion reports production of neurons in the injured mouse brain. This supports reprogramming after injury, but the paper does not establish that the reprogramming was transient or that it improved tissue repair; the Discussion also warns that cell overgrowth and tumorigenesis prevent clinical application. Skin wound healing is attributed to a different citation in the citing sentence. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Metadata

Authors
Gao, X., Wang, X., Xiong, W., & Chen, J.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2016-03-09
Volume
6
Issue
1
ISSN
2045-2322
DOI
10.1038/srep22490
PMC
PMC4783661
Cited by
73
References
6
Language
en
Licence

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