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Brain repair and reprogramming : the route to clinical translation

Grealish, S. LU ; Drouin-Ouellet, J. LU and Parmar, M. LU (2016) In Journal of Internal Medicine 280(3). p.265-275
Abstract

The adult brain has a very limited capacity for generation of new neurons, and neurogenesis only takes place in restricted regions. Some evidence for neurogenesis after injury has been reported, but few, if any, neurons are replaced after brain injury or degeneration, and the permanent loss of neurons leads to long-term disability and loss of brain function. For decades, researchers have been developing cell transplantation using exogenous cell sources for brain repair, and this method has now been shown to successfully restore lost function in experimental and clinical trials. Here, we review the development of cell-replacement strategies for brain repair in Parkinson's disease using the example of human foetal brain cells being... (More)

The adult brain has a very limited capacity for generation of new neurons, and neurogenesis only takes place in restricted regions. Some evidence for neurogenesis after injury has been reported, but few, if any, neurons are replaced after brain injury or degeneration, and the permanent loss of neurons leads to long-term disability and loss of brain function. For decades, researchers have been developing cell transplantation using exogenous cell sources for brain repair, and this method has now been shown to successfully restore lost function in experimental and clinical trials. Here, we review the development of cell-replacement strategies for brain repair in Parkinson's disease using the example of human foetal brain cells being successfully translated from preclinical findings to clinical trials. These trials demonstrate that cell-replacement therapy is a viable option for patients with Parkinson's disease, but more importantly also show how the limited availability of foetal cells calls for development of novel cell sources and methods for generating new neurons for brain repair. We focus on new stem cell sources that are on the threshold of clinical application for brain repair and discuss emerging cellular reprogramming technologies. Reviewing the current status of direct neural conversion, both in vitro and in vivo, where somatic cells are directly reprogrammed into functional neurons without passing through a stem cell intermediate, we conclude that both methods result in the successful replacement of new neurons that mature and integrate into the host brain. Thus, this new field shows great promise for future brain repair, although much work is still needed in preclinical animal models before it can be seriously considered for clinical applications.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
brain repair, human embryonic stem cells, induced neurons, in vivo reprogramming, Parkinson's disease, Reprogramming, transplantation
in
Journal of Internal Medicine
volume
280
issue
3
pages
11 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:84983070814
ISSN
0954-6820
DOI
10.1111/joim.12475
language
English
LU publication?
yes
id
ccc0f6dd-3736-4080-8f25-52f2c77e37a2
date added to LUP
2016-09-01 15:13:30
date last changed
2017-02-12 04:35:02
@article{ccc0f6dd-3736-4080-8f25-52f2c77e37a2,
  abstract     = {<p>The adult brain has a very limited capacity for generation of new neurons, and neurogenesis only takes place in restricted regions. Some evidence for neurogenesis after injury has been reported, but few, if any, neurons are replaced after brain injury or degeneration, and the permanent loss of neurons leads to long-term disability and loss of brain function. For decades, researchers have been developing cell transplantation using exogenous cell sources for brain repair, and this method has now been shown to successfully restore lost function in experimental and clinical trials. Here, we review the development of cell-replacement strategies for brain repair in Parkinson's disease using the example of human foetal brain cells being successfully translated from preclinical findings to clinical trials. These trials demonstrate that cell-replacement therapy is a viable option for patients with Parkinson's disease, but more importantly also show how the limited availability of foetal cells calls for development of novel cell sources and methods for generating new neurons for brain repair. We focus on new stem cell sources that are on the threshold of clinical application for brain repair and discuss emerging cellular reprogramming technologies. Reviewing the current status of direct neural conversion, both in vitro and in vivo, where somatic cells are directly reprogrammed into functional neurons without passing through a stem cell intermediate, we conclude that both methods result in the successful replacement of new neurons that mature and integrate into the host brain. Thus, this new field shows great promise for future brain repair, although much work is still needed in preclinical animal models before it can be seriously considered for clinical applications.</p>},
  author       = {Grealish, S. and Drouin-Ouellet, J. and Parmar, M.},
  issn         = {0954-6820},
  keyword      = {brain repair,human embryonic stem cells,induced neurons,in vivo reprogramming,Parkinson's disease,Reprogramming,transplantation},
  language     = {eng},
  month        = {09},
  number       = {3},
  pages        = {265--275},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Internal Medicine},
  title        = {Brain repair and reprogramming : the route to clinical translation},
  url          = {http://dx.doi.org/10.1111/joim.12475},
  volume       = {280},
  year         = {2016},
}