Neural stem cell transplant survival in brains of mice: assessing the effect of immunity and ischemia by using real-time bioluminescent imaging.
OBJECTIVE
To use bioluminescent imaging in a murine transplant model to monitor the in vivo responses of transplanted luciferase-gene-positive neural progenitor cells (NPCs) to host immunity and ischemia.


METHODS
All animal studies were conducted according to institutional guidelines, with approval of the Subcommittee on Research Animal Care. Cranial windows were created in all animals, and all animals underwent NPC (C17.2-Luc-GFP-gal) transplantation into the right basal ganglia. An observational study was performed on C57 BL/6 (n = 5), nude (n = 4), and CD-1 (n = 4) mice, with bioluminescent imaging performed at days 7, 11, and 14 after transplantation. A study on the effects of ischemia was performed in a similar manner, but with the following differences: On day 9 after transplantation, the C57 BL/6 mice underwent 18 minutes of transient forebrain ischemia by means of temporary bilateral carotid occlusions (n = 6). A control group of C57 BL/6 mice underwent sham surgery (n = 6). Bioluminescent imaging was performed on the ischemic animals and control animals at days 7, 9, 11, and 14. Repeated-measures analysis of variance or Student t test was used to compare the means of the luciferase activities.


RESULTS
In vivo cell tracking demonstrated that (a) C17.2-Luc-GFP-gal NPCs survived and proliferated better in the T-cell deficient nude mice than in the immunocompetent C57 BL/6 or CD-1 mice, in which progressive immune mediated cell loss was shown, and (b) transient forebrain ischemia appeared, unexpectedly, to act as a short-term stimulus to transplanted NPC growth and survival in immunocompetent mice.


CONCLUSIONS
Immune status and host immunity can have an influence on NPC graft survival, and these changes can be noninvasively assessed with bioluminescent imaging in this experimental model.
Kim
Dong-Eog
DE
Department of Neurology, DongGuk University International Hospital, Goyang City, Gyeonggi-do, Korea [corrected]
Tsuji
Kiyoshi
K
Kim
Young Ro
YR
Mueller
Franz-Josef
FJ
Eom
Hyeon-Seok
HS
Snyder
Evan Y
EY
Lo
Eng H
EH
Weissleder
Ralph
R
Schellingerhout
Dawid
D
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology*; D002545:Brain Ischemia / Q000175:diagnosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000276:immunology
D008156:Luciferases