In vivo bioluminescence imaging of cord blood derived mesenchymal stem cell transplantation into rat myocardium

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Min, Jung-Joon; Ahn, Youngkeun; Moon, Sungmin; Kim, Yong Sook; Park, Jong Eun; Kim, Sung Mi; Le, Uyenchi N.; Wu, Joseph C.; Joo, Soo Yeon; Hong, Moon Hwa; Yang, Deok Hwan; Jeong, Myung Ho; Song, Chang Hun; Jeong, Yun Hyeok; Yoo, Kyung Yeon; Kang, Kyung-Sun; Bom, Hee-Seung
Issue Date
Springer Verlag
Ann Nucl Med. 2006; 20: 165-170
cord bloodmesenchymal stem cellbioluminescencemolecular imaging
The conventional method for the analysis of myocardial cell transplantation depends on
postmortem histology. Here, we have sought to demonstrate the feasibility of a longitudinal
monitoring of transplanted cell survival in living animals, accomplished with optical imaging
techniques and pharmacological interventions. Methods: Human cord blood (50 ml) was donated
with parental consent. After getting cord blood derived mesenchymal stem cells (CBMSCs), cells
were transfected (MOI = 100) overnight with adenovirus encoding firefly luciferase gene (Ad-
CMV-Fluc). Our experimental Sprague-Dawley rats (n = 12) were given intramyocardial injections
containing 1 × 106 CBMSCs, which had been made to express the firefly luciferase (Fluc) reporter
gene. Optical bioluminescence imaging was then conducted using a cooled charged-coupled device
(CCD) camera (Xenogen), beginning on the day after the transplantation (day 1). Groups of mice
were intraperitoneally injected with cyclosporine (5 mg/kg) or tacrolimus (1 mg/kg), in an attempt
to determine the degree to which cell survival had been prolonged, and these values were then
compared with the cell survival values of the negative control group. The presence of transplanted
CBMSCs on in vivo images confirmed by in situ hybridization for human specific Alu in the
myocardium. Results: Cardiac bioluminescence signals were determined to be present for 6 days
after transplantation: day 1 (97000 ± 9100 × 105 p/s/cm2/sr), day 3 (9600 ± 1110 p/s/cm2/sr), and
day 5 (3200 ± 550 p/s/cm2/sr). The six mice that received either cyclosporine or tacrolimus
displayed cardiac bioluminescence signals for a period of 8 days after transplantation. We observed
significant differences between the treated group and the non-treated group, beginning on day 3
(tacrolimus; 26500 ± 4340 p/s/cm2/sr, cyclosporine; 27200 ± 3340 p/s/cm2/sr, non-treated; 9630 ±
1180 p/s/cm2/sr, p < 0.01), and persisting until day 7 (tacrolimus; 12500 ± 2946 p/s/cm2/sr,
cyclosporine; 7310 ± 1258 p/s/cm2/sr, non-treated; 2460 ± 160 p/s/cm2/sr, p < 0.01). The humanderived
CBMSCs were detected in the myocardium 3 days after transplantation by in situ
hybridization. Conclusions: The locations, magnitude, and survival duration of the CBMSCs were
noninvasively monitored with a bioluminescence optical imaging system. We determined that
optical molecular imaging expedites the fast throughput screening of pharmaceutical agents,
allowing for the noninvasive tracking of cell survival within animals. In rat cardiac CBMSC
transplant models, transient immunosuppressive treatment with tacrolimus or cyclosporine was
shown to improve donor cell survival.
0914-7187 (print)
1864-6433 (online)
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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