Reduced xenograft rejection in rat striatum after pretransplant photodynamic therapy of murine neural xenografts.
OBJECTIVE
The goal of this study was to develop a method of reducing neural xenograft rejection by pretreating the graft with photodynamic therapy (PDT).


METHODS
Xenograft cell suspensions were prepared from fetal mouse mesencephalon, after which they were incubated for 30 minutes with various concentrations of a photosensitizer, verteporfin for injection, and light exposure. The xenograft cell suspensions were injected into the dopamine-depleted striata of 40 hemiparkinsonian rats assigned to different treatment groups. Four weeks after transplantation, xenograft function (determined by methamphetamine-induced rotation) and survival (determined by immunohistochemical staining for murine neurons) were compared. Group 1 animals (xenografts pretreated with 25 ng/ml verteporfin) and Group 3 animals (no verteporfin pretreatment, but daily administration of cyclosporin A) had significantly better xenograft survival and function compared with control animals (no pretreatment with verteporfin). Group 2 animals (xenografts pretreated with 250 ng/ml verteporfin) had no significant improvement.


CONCLUSIONS
This work demonstrates improved neural xenograft survival and function when using pretransplant PDT of the graft in a rodent model. The potential benefits of this new therapy are its convenience (one pretransplant treatment) and its compatibility with host immunosuppression.
Honey
C R
CR
Department of Immunology and Microbiology, University of British Columbia, Vancouver, Canada. choney@interchange.ubc.ca
Obochi
M O
MO
Shen
H
H
Margaron
P
P
Yip
S
S
Levy
J G
JG
D000704:Analysis of Variance; D000818:Animals; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D016572:Cyclosporine / Q000627:therapeutic use; D004298:Dopamine / Q000172:deficiency; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism / Q000601:surgery; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011166:Porphyrins / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014183:Transplantation, Heterologous; D000077362:Verteporfin
D007166:Immunosuppressive Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D016572:Cyclosporine; D004298:Dopamine