Establishment of a bioluminescent imaging-based in vivo leukemia model by intra-bone marrow injection

Lee,Myoung  Woo; Kim,Hye  Jin; Yoo,Keon  Hee; Kim,Dae  Seong; Yang,Jin  Mo; Kim,Hye  Ryung; Noh,Yoo  Hun; Baek,Hyunjung; Kwon,Heechung; Son,Meong  Hi; Lee,Soo  Hyun; Cheuh,Hee  Won; Jung,Hye  Lim; Sung,Ki  Woong; Koo,Hong  Hoe

doi:10.3892/ijo.2012.1634

Establishment of a bioluminescent imaging-based in vivo leukemia model by intra-bone marrow injection

Authors:
- Myoung Woo Lee
- Hye Jin Kim
- Keon Hee Yoo
- Dae Seong Kim
- Jin Mo Yang
- Hye Ryung Kim
- Yoo Hun Noh
- Hyunjung Baek
- Heechung Kwon
- Meong Hi Son
- Soo Hyun Lee
- Hee Won Cheuh
- Hye Lim Jung
- Ki Woong Sung
- Hong Hoe Koo
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Affiliations: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Division of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea, Department of Pediatrics, Dong-A Medical Center, Dong-A University College of Medicine, Busan, Republic of Korea
Published online on: September 20, 2012 https://doi.org/10.3892/ijo.2012.1634
Pages: 2047-2056

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Abstract

In vivo leukemia mouse models are usually generated by intraperitoneal (IP) or intravenous (IV) injection of leukemia cells. However, the pattern of leukemia development observed can be inconsistent. This study investigated injection directly into bone marrow [intra-bone marrow transplantation (IBMT)], the natural microenvironment of leukemia. A bioluminescent imaging-based leukemia animal model has been established by direct injection of a bioluminescent leukemia cells (CCRF-CEM/fLuc) into NOD/SCID mouse tibia bone marrow and compared with models established by IP and IV routes. The comparison revealed that a bioluminescent in vivo leukemia model established via IBMT could recapitulate leukemia more faithfully and facilitate improved quantification of leukemia engraftment kinetics with a wider range of bioluminescent intensity than IP or IV. IBMT of bioluminescent leukemic cells allowed quantification of dose-dependent responses to anti-leukemic drugs, thus validating this model as a potential preclinical anti-leukemic drug screening system. IBMT-leukemia cells isolated from peripheral blood of the model mice and then injected into new recipients successfully established a second generation IBMT in vivo model and demonstrated the reproducibility of the model. Bioluminescent imaging-based analysis of this IBMT-leukemia model could provide a means for the comprehensive evaluation of treatment responses with enhanced sensitivity in preclinical studies.

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