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Real-time in vivo monitoring of viable stem cells implanted on biocompatible scaffolds

Cited 27 time in Web of Science Cited 32 time in Scopus
Authors
Hwang, Do Won; Jang, Sung June; Kim, Yun Hui; Kim, Hyun Joo; Shim, In Kyong; Jeong, Jae Min; Chung, June-Key; Lee, Myung Chul; Lee, Seung Jin; Kim, Seung U; Kim, Soonhag; Lee, Dong Soo
Issue Date
2008-04-26
Publisher
Springer Verlag
Citation
Eur J Nucl Med Mol Imaging. 2008;35(10):1887-98
Keywords
AnimalsAutoradiography/*methodsCell Culture Techniques/*methodsCell LineComputer SystemsLuminescent Measurements/*methodsMiceMice, Inbred BALB CMice, Nude*Molecular Probe TechniquesStem Cell Transplantation/*methodsStem Cells/*cytology/*radionuclide imagingTissue Engineering/*methodsWhole Body Imaging/*methods
Abstract
PURPOSE: Three-dimensional fibrous scaffolds provide an environment that enhances transplanted stem cell survival in vivo and facilitates imaging their localization, viability, and growth in vivo. To assess transplanted stem cell viability on biocompatible polymer scaffolds in vivo, we developed in vivo imaging systems for evaluation of implanted viable neural stem cells (NSC) and mesenchymal stem cells (MSC) on scaffolds using luciferase or sodium/iodide symporter (NIS) genes. METHODS: Firefly luciferase stably expressing-C6 cell was established (C6-Fluc). The human neural stem cell, F3, was infected with adenoviral vector carrying luciferase gene (F3-Fluc) and MSC expressing NIS controlled by ubiquitin C promoter using lentiviral vector was established by treating blasticidine for 2 weeks (MSC-NIS). Chitosan and poly L-lactic acid (PLLA) scaffolds were used for in vivo image. In vivo expression of luciferase and human NIS was examined by bioluminescence image or (99m)Tc-pertechnetate gamma camera image, respectively. The cell/scaffold complex was implanted into subcutaneous or abdominal area of BALB/C nude mouse. For quantitative evaluation of cell viability, regions of interest were drawn on (99m)Tc-pertechnetate scintigraphy by manual. RESULTS: The gradual increase of luciferase activity was observed in C6-Fluc seeded with chitosan according to the increase in the number of cells. C6-Fluc/chitosan complex subcutaneously implanted into nude mice showed longitudinal bioluminescence image until 34 days. Luciferase image of abdominal-injected C6-Fluc/PLLA complex was saturated in only 14 days, showing great cell growth due to abundant nutrients. F3 cells showed well-incorporated pattern with fibrous chitosan scaffold using scanning electron microscopy. F3 infected with Ad-Fluc showed >100-fold higher luciferase activity than luciferase activity in F3. Cell-number-dependent increase of luciferase activity was shown in F3-Fluc seeded on chitosan. F3-Fluc incorporation into chitosan after abdominal injection was clearly visible on bioluminescence image up to 11 days. Radionuclide imaging showed higher uptake by MSC-NIS on PLLA scaffolds than by MSC-NIS not seeded on a scaffold. Quantitative data showed significantly better survival of MSC-NIS on PLLA scaffolds than without scaffold at 72 h post-implantation, which concurred with histologic findings. CONCLUSION: These results suggest that NSC-Fluc and MSC-NIS cells incorporated within polymer scaffolds can be monitored on a long-term basis by serial in vivo imaging. We believe that a biocompatible scaffold-based imaging system could be used to assess stem cell viabilities in a non-invasive way to aid the development of regenerative therapeutics.
ISSN
1619-7070 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18437378

http://www.springerlink.com/content/b108181wx4m14852/fulltext.pdf

http://hdl.handle.net/10371/67780
DOI
https://doi.org/10.1007/s00259-008-0751-z
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College of Medicine/School of Medicine (의과대학/대학원)Nuclear Medicine (핵의학전공)Journal Papers (저널논문_핵의학전공)
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