Using C-arm x-ray imaging to guide local reporter probe delivery for tracking stem cell engraftment Journal Article

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Authors: Kedziorek, D. A.; Solaiyappan, M.; Walczak, P.; Ehtiati, T.; Fu, Y; Bulte, J. W.; Shea, S. M.; Brost, A.; Wacker, F. K.; Kraitchman, D. L.
Article Title: Using C-arm x-ray imaging to guide local reporter probe delivery for tracking stem cell engraftment
Abstract: Poor cell survival and difficulties with visualization of cell delivery are major problems with current cell transplantation methods. To protect cells from early destruction, microencapsulation methods have been developed. The addition of a contrast agent to the microcapsule also could enable tracking by MR, ultrasound, and X-ray imaging. However, determining the cell viability within the microcapsule still remains an issue. Reporter gene imaging provides a way to determine cell viability, but delivery of the reporter probe by systemic injection may be hindered in ischemic diseases. In the present study, mesenchymal stem cells (MSCs) were transfected with triple fusion reporter gene containing red fluorescent protein, truncated thymidine kinase (SPECT/PET reporter) and firefly luciferase (bioluminescence reporter). Transfected cells were microencapsulated in either unlabeled or perfluorooctylbromide (PFOB) impregnated alginate. The addition of PFOB provided radiopacity to enable visualization of the microcapsules by X-ray imaging. Before intramuscular transplantation in rabbit thigh muscle, the microcapsules were incubated with D-luciferin, and bioluminescence imaging (BLI) was performed immediately. Twenty-four and forty-eight hours post transplantation, c-arm CT was used to target the luciferin to the X-ray-visible microcapsules for BLI cell viability assessment, rather than systemic reporter probe injections. Not only was the bioluminescent signal emission from the PFOB-encapsulated MSCs confirmed as compared to non-encapsulated, naked MSCs, but over 90% of injection sites of PFOB-encapsulated MSCs were visible on c-arm CT. The latter aided in successful targeting of the reporter probe to injection sites using conventional X-ray imaging to determine cell viability at 1-2 days post transplantation. Blind luciferin injections to the approximate location of unlabeled microcapsules resulted in successful BLI signal detection in only 18% of injections. In conclusion, reporter gene probes can be more precisely targeted using c-arm CT for in vivo transplant viability assessment, thereby avoiding large and costly systemic injections of a reporter probe.
Journal Title: Theranostics
Volume: 3
Issue: 11
ISSN: 1838-7640; 1838-7640
Publisher: Unknown  
Journal Place: Australia
Date Published: 2013
Start Page: 916
End Page: 926
Language: eng
DOI/URL:

10.7150/thno.6943
Notes: GR: NIH R21-HL89029/HL/NHLBI NIH HHS/United States; JID: 101552395; 0 (Luminescent Proteins); 0 (red fluorescent protein); EC 1.13.12.7 (Luciferases, Firefly); EC 2.7.1.21 (Thymidine Kinase); OID: NLM: PMC3879108; OTO: NOTNLM; 2013 [ecollection]; 2013/06/18 [received]; 2013/11/28 [accepted]; 2013/12/17 [epublish]; epublish