HESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation
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HESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation. / Heuer, Andreas; Jönsson, Marie E.; Pfisterer, Ulrich; Kirkeby, Agnete; Parmar, Malin.
In: Experimental Neurology, Vol. 282, 01.08.2016, p. 78-85.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - HESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation
AU - Heuer, Andreas
AU - Jönsson, Marie E.
AU - Pfisterer, Ulrich
AU - Kirkeby, Agnete
AU - Parmar, Malin
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Cyclosporine
KW - Desensitisation
KW - HESC
KW - Immune response
KW - Rejection
KW - Stem cell
KW - Transplant
KW - Xenograft
UR - http://www.scopus.com/inward/record.url?scp=84969752910&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2016.05.027
DO - 10.1016/j.expneurol.2016.05.027
M3 - Journal article
C2 - 27235932
AN - SCOPUS:84969752910
VL - 282
SP - 78
EP - 85
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
ER -
ID: 228505407