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DOI: 10.1148/radiol.2413050466
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(Radiology 2006;241:822-830.)
© RSNA, 2006

Molecular Imaging

Neural Stem Cell Transplant Survival in Brains of Mice: Assessing the Effect of Immunity and Ischemia by using Real-time Bioluminescent Imaging1

Dong-Eog Kim, MD, PhD2, Kiyoshi Tsuji, MD, Young Ro Kim, PhD, Franz-Josef Mueller, MD, Hyeon-Seok Eom, MD, PhD3, Evan Y. Snyder, MD, PhD, Eng H. Lo, PhD, Ralph Weissleder, MD, PhD and Dawid Schellingerhout, MBChB

1 From the Center for Molecular Imaging Research (D.E.K., R.W., D.S.), Neuroprotection Research Laboratory (K.T., E.H.L.), and NMR Center, Department of Radiology (Y.R.K.), Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass; Program in Developmental & Regenerative Cell Biology, Burnham Institute, La Jolla, Calif (F.J.M., E.Y.S.); and Catholic Hematopoietic Stem Cell Transplantation Center, Catholic University of Korea, Seoul, Korea (H.S.E.). Received March 18, 2005; revision requested May 19; revision received August 4; accepted September 1; final version accepted March 6, 2006. D.S. supported in part by grants from the Radiological Society of North America Research and Education Foundation and the American Brain Tumor Association. Address correspondence to D.S., Neuroradiology Section, Departments of Radiology and Experimental Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, Box 57, 1515 Holcombe Blvd, Houston, TX 77030 (e-mail: dawid.schellingerhout{at}di.mdacc.ut.edu).

Purpose: 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.

Materials and 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.

Conclusion: 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.

© RSNA, 2006




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