Survival of transplanted human neural stem cell line (ReNcell VM) into the rat brain with and without immunosuppression.
Functional replacement of specific neuronal populations through transplantation of neural tissue represents an attractive therapeutic strategy for treating neurodegenerative disorders like Parkinson's disease (PD). Even though the brain is a partially immune privileged site, immunosuppression is still needed for the prevention of host immune response, and thus, xenograft rejection. Here, we investigated the fate of human ventral mesencephalon derived immortalized cell line ReNcell VM upon unilateral transplantation into the intact rat striatum with or without immunosuppression with cyclosporine A (CsA). The status of xenografted human ReNcell VM cells was analysed by immunohistochemistry/immunofluorescence 4 and 6weeks after transplantation. Four weeks after transplantation, ReNcell VM cells could be detected in both groups, although the number of survived cells was significantly higher in brains of immunosuppressed rats. In contrast, only 2 out of 6 brains grafted without immunosuppression revealed human ReNcell VM cells 6weeks post grafting, whereas a considerable number of human cells could still be found in all the brains of immunosuppressed rats. Immunohistochemical analysis of grafted cells showed almost no evidence of neuronal differentiation, but rather astroglial development. In summary, we have shown that the immunosuppression is needed for the survival of human VM derived progenitor cells in the rat striatum. CsA affected cell survival, but not differentiation capacity: in both groups, grafted either with or without immunosuppression, the ReNcell VM cells lacked neuronal phenotype and developed preferentially into astroglia.
Department of Anatomy, University of Rostock, Germany.
M
M
Hovakimyan
J
J
Müller
A
A
Wree
S
S
Ortinau
A
A
Rolfs
O
O
Schmitt
D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D003470:Culture Media; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D017072:Neostriatum / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000637:transplantation*; D020543:Proteome / Q000235:genetics; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods*
D034961:Antigens, Nuclear; D003470:Culture Media; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D020543:Proteome; C506808:neuronal nuclear antigen NeuN, human