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Biodistribution and in vivo efficacy of genetically modified human mesenchymal stem cells systemically transplanted into a mouse bone fracture model

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Abstract

Human mesenchymal stem cells (hMSCs) have generated a great deal of interest in clinical application due to their ability to undergo multi-lineage differentiation. Recently, ex vivo genetic modification of hMSCs was attempted to increase their differentiation potential. The present study was conducted to evaluate the biodistribution and in vivo efficacy of genetically modified hMSCs. To accomplish this, Runx2, which is a key transcription factor associated with osteoblast differentiation, was transduced into hMSCs using lentiviral vectors expressing green fluorescent protein (GFP) or luciferase. Here, we developed an experimental fracture in mice femur to investigate the effects of Runx2-transduced hMSCs on bone healing and migration into injury site. We conducted bio-luminescence imaging (BLI) using luciferase-tagged vector and quantitative real-time PCR using GFP probe to investigate the biodistribution of Runx2-transduced hMSCs in the fracture model. The biodistribution of hMSC cells in the fractured femur was observed at 14 days post-transplantation upon both BLI imaging and real-time PCR. Moreover, the fractured mice transplanted with Runx2-transduced hMSCs showed superior bone healing when compared to mock-transduced hMSC and MRC5 fibroblasts which were used as control. These data suggested that transplanted genetically modified hMSCs systemically migrate to the fractured femur, where they contribute to bone formation in vivo.

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Acknowledgments

This study was supported by a grant (08171KFDA512) from the Korea Food and Drug Administration, Republic of Korea.

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Authors and Affiliations

  1. Biotechnological Development Assistance Team, National Institute of Food and Drug Safety Evaluation, Korea Food & Drug Administration, Osong Health Technology Administration Complex, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chengwon-gun, Chungcheongbuk-do, 363-700, Republic of Korea

    Jin Wook Kang, Ki Dae Park, Youngju Choi, Dae Hyun Baek, Jae Hyun Park, Kyoung Suk Choi, Hyung Soo Kim & Tae Moo Yoo

  2. Department of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Korea Food & Drug Administration, Chengwon-gun, Republic of Korea

    Wan-Seob Cho & Mina Choi

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  1. Jin Wook Kang
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  2. Ki Dae Park
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  3. Youngju Choi
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  5. Wan-Seob Cho
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  9. Hyung Soo Kim
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  10. Tae Moo Yoo
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Correspondence to Tae Moo Yoo.

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Kang, J.W., Park, K.D., Choi, Y. et al. Biodistribution and in vivo efficacy of genetically modified human mesenchymal stem cells systemically transplanted into a mouse bone fracture model. Arch. Pharm. Res. 36, 1013–1022 (2013). https://doi.org/10.1007/s12272-013-0132-4

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  • DOI: https://doi.org/10.1007/s12272-013-0132-4

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