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HESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation

Heuer, Andreas LU ; Kirkeby, Agnete LU ; Pfisterer, Ulrich LU ; Jönsson, Marie E. LU and Parmar, Malin LU (2016) In Experimental Neurology 282. p.78-85
Abstract

Stem cell therapies for neurological disorders are rapidly moving towards use in clinical trials. Before initiation of clinical trials, extensive pre-clinical validation in appropriate animal models is essential. However, grafts of human cells into the rodent brain are rejected within weeks after transplantation and the standard methods of immune-suppression for the purpose of studying human xenografts are not always sufficient for the long-term studies needed for transplanted human neurons to maturate, integrate and provide functional benefits in the host brain. Neonatal injections in rat pups using human fetal brain cells have been shown to desensitise the host to accept human tissue grafts as adults, whilst not compromising their... (More)

Stem cell therapies for neurological disorders are rapidly moving towards use in clinical trials. Before initiation of clinical trials, extensive pre-clinical validation in appropriate animal models is essential. However, grafts of human cells into the rodent brain are rejected within weeks after transplantation and the standard methods of immune-suppression for the purpose of studying human xenografts are not always sufficient for the long-term studies needed for transplanted human neurons to maturate, integrate and provide functional benefits in the host brain. Neonatal injections in rat pups using human fetal brain cells have been shown to desensitise the host to accept human tissue grafts as adults, whilst not compromising their immune system. Here, we show that differentiated human embryonic stem cells (hESCs) can be used for desensitisation to achieve long-term graft survival of human stem cell-derived neurons in a xenograft setting, surpassing the time of conventional pharmacological immune-suppressive treatments. The use of hESCs for desensitisation opens up for a widespread use of the technique, which will be of great value when performing pre-clinical evaluation of stem cell-derived neurons in animal models.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cyclosporine, Desensitisation, HESC, Immune response, Rejection, Stem cell, Transplant, Xenograft
in
Experimental Neurology
volume
282
pages
8 pages
publisher
Academic Press
external identifiers
  • Scopus:84969752910
  • WOS:000378460200009
ISSN
0014-4886
DOI
10.1016/j.expneurol.2016.05.027
language
English
LU publication?
yes
id
634a36c9-4789-4e3c-8acc-3ea1f6c1a268
date added to LUP
2016-07-18 14:20:10
date last changed
2017-01-01 08:30:43
@article{634a36c9-4789-4e3c-8acc-3ea1f6c1a268,
  abstract     = {<p>Stem cell therapies for neurological disorders are rapidly moving towards use in clinical trials. Before initiation of clinical trials, extensive pre-clinical validation in appropriate animal models is essential. However, grafts of human cells into the rodent brain are rejected within weeks after transplantation and the standard methods of immune-suppression for the purpose of studying human xenografts are not always sufficient for the long-term studies needed for transplanted human neurons to maturate, integrate and provide functional benefits in the host brain. Neonatal injections in rat pups using human fetal brain cells have been shown to desensitise the host to accept human tissue grafts as adults, whilst not compromising their immune system. Here, we show that differentiated human embryonic stem cells (hESCs) can be used for desensitisation to achieve long-term graft survival of human stem cell-derived neurons in a xenograft setting, surpassing the time of conventional pharmacological immune-suppressive treatments. The use of hESCs for desensitisation opens up for a widespread use of the technique, which will be of great value when performing pre-clinical evaluation of stem cell-derived neurons in animal models.</p>},
  author       = {Heuer, Andreas and Kirkeby, Agnete and Pfisterer, Ulrich and Jönsson, Marie E. and Parmar, Malin},
  issn         = {0014-4886},
  keyword      = {Cyclosporine,Desensitisation,HESC,Immune response,Rejection,Stem cell,Transplant,Xenograft},
  language     = {eng},
  month        = {08},
  pages        = {78--85},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {HESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2016.05.027},
  volume       = {282},
  year         = {2016},
}