Sustained survival of xenografted human neural stem/progenitor cells in experimental brain trauma despite discontinuation of immunosuppression.
Neural stem cells have emerged as a promising therapeutic tool in CNS disease and injuries. In the clinical setting, cultured human neural stem/progenitor cells (hNSC) are an attractive possibility for transplantation to the damaged brain. However, transplantation of hNSC requires toxic immunosuppressive treatment to avoid rejection. The aim of the current study was to evaluate if shortening the duration of immunosuppression by cyclosporin A would affect hNSC survival and differentiation after transplantation to the site of a focal brain injury in the rat. hNSC were xenografted to the hippocampus and the medial limit of an experimentally induced cortical contusion. The animals received immunosuppression for either 6 or 3 weeks or no immunosuppression. The status of the grafted human cells was analysed by immunohistochemistry. No statistically significant differences were observed between the two immunosuppressed groups regarding graft survival, migration or proliferation at 6 weeks post-transplantation. In contrast, the graft survival was extremely poor in the non-immunosuppressed group. Furthermore, the expression of the differentiation markers nestin, neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) in the transplanted cells did not differ significantly between the two immunosuppressed groups. Moreover, a fourth group of eight animals that were immunosuppressed for 3 weeks were allowed to survive for 6 months. Five of these rats demonstrated robust graft survival in the hippocampus and scattered cells in the cortex. This study demonstrates the importance of immunosuppression but also the possibility of shortening immunosuppression without impacting on the phenotype of the grafted hNSC.
Wennersten
André
A
Department of Clinical Neuroscience, Section of Clinical CNS Research, Karolinska Institutet, S-171 76 Stockholm, Sweden. andre.wennersten@ki.se
Holmin
Staffan
S
Al Nimer
Faiez
F
Meijer
Xia
X
Wahlberg
Lars U
LU
Mathiesen
Tiit
T
D000818:Animals; D001930:Brain Injuries / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D005333:Fetus; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007165:Immunosuppression Therapy / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D014183:Transplantation, Heterologous / Q000379:methods*
D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins