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BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells

Gene Therapy volume 20, pages 370–377 (2013)Cite this article

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Abstract

Bone regeneration achieved using mesenchymal stem cells (MSCs) and nonviral gene therapy holds great promise for patients with fractures seemingly unable to heal. Previously, MSCs overexpressing bone morphogenetic proteins (BMPs) were shown to differentiate into the osteogenic lineage and induce bone formation. In the present study, we evaluated the potential of osteogenic differentiation in porcine adipose tissue- and bone marrow-derived MSCs (ASCs and BMSCs, respectively) in vitro and in vivo when induced by nucleofection with rhBMP-2 or rhBMP-6. Our assessment of the in vivo efficiency of this procedure was made using quantitative micro-computed tomography (micro-CT). Nucleofection efficiency and cell viability were similar in both cell types; however, the micro-CT analyses demonstrated that in both ASCs and BMSCs, nucleofection with rhBMP-6 generated bone tissue faster and of higher volumes than nucleofection with rhBMP-2. RhBMP-6 induced more efficient osteogenic differentiation in vitro in BMSCs, and in fact, greater osteogenic potential was identified in BMSCs both in vitro and in vivo than in ASCs. On the basis of our findings, we conclude that BMSCs nucleofected with rhBMP-6 are superior at inducing bone formation in vivo than all other groups studied.

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Acknowledgements

We acknowledge partial funding from the Telemedicine and Advanced Technology Research Center (TATRC), the US Army Medical Research and Materiel Command (Grant no. 0821700) and the Israel Ministry of Science and Technology (Grant no. 3-6446 and a ‘Levi Eshkol’ fellowship to IK).’

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  1. O Mizrahi and D Sheyn: These authors contributed equally to this work.

Authors and Affiliations

  1. Skeletal Biotech Laboratory, Hebrew University-Hadassah, Faculty of Dental Medicine, Jerusalem, Israel

    O Mizrahi, I Kallai, D Gazit & Z Gazit

  2. Department of Surgery, Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA, USA

    D Sheyn, W Tawackoli, A Oh, S Su, X Da, P Zarrini, D Gazit & Z Gazit

  3. Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA

    G Cook-Wiens

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Correspondence to Z Gazit.

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Mizrahi, O., Sheyn, D., Tawackoli, W. et al. BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells. Gene Ther 20, 370–377 (2013). https://doi.org/10.1038/gt.2012.45

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