Transplantation of neural stem cells in a rat model of stroke: assessment of short-term graft survival and acute host immunological response.
The use of progenitors and stem cells for neural grafting is promising, as these not only have the potential to be maintained in vitro until use, but may also prove less likely to evoke an immunogenic response in the host, when compared to primary (fetal) grafts. We investigated whether the short-term survival of a grafted conditionally immortalised murine neuroepithelial stem cell line (MHP36) (2 weeks post-implantation, 4 weeks post-ischaemia) is influenced by: (i) immunosuppression (cyclosporin A (CSA) vs. no CSA), (ii) the local (intact vs. lesioned hemisphere), or (iii) global (lesioned vs. sham) brain environment. MHP36 cells were transplanted ipsi- and contralateral to the lesion in rats with middle cerebral artery occlusion (MCAo) or sham controls. Animals were either administered CSA or received no immunosuppressive treatment. A proliferation assay of lymphocytes dissociated from cervical lymph nodes, grading of the survival of the grafted cells, and histological evaluation of the immune response revealed no significant difference between animals treated with or without CSA. There was no difference in survival or immunological response to cells grafted ipsi- or contralateral to the lesion. Although a local upregulation of immunological markers (MHC class I, MHC class II, CD45, CD11b) was detected around the injection site and the ischaemic lesion, these were not specifically upregulated in response to transplanted cells. These results provide evidence for the low immunogenic properties of MHP36 cells during the initial period following implantation, known to be associated with an acute host immune response and ensuing graft rejection.
Modo
Michel
M
Neuroimaging Research Group-Neurology P042, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. m.modo@iop.kcl.ac.uk
Rezaie
Payam
P
Heuschling
Paul
P
Patel
Sara
S
Male
David K
DK
Hodges
Helen
H
D000818:Animals; D015415:Biomarkers; D016380:Brain Tissue Transplantation; D002461:Cell Line, Transformed / Q000276:immunology / Q000637:transplantation*; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009474:Neurons / Q000276:immunology / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D020521:Stroke / Q000628:therapy*
D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine