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Enhanced bone morphogenic protein adenoviral gene delivery to bone marrow stromal cells using magnetic nanoparticle

  • Lee, Jung-Tae (Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University) ;
  • Jung, Jae-Whan (Department of Biochemistry, Kyungpook National University School of Medicine) ;
  • Choi, Jae-Yong (Department of Biochemistry, Kyungpook National University School of Medicine) ;
  • Kwon, Tae-Geon (Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University)
  • Received : 2013.03.21
  • Accepted : 2013.05.10
  • Published : 2013.06.30

Abstract

Objectives: This study investigated the question of whether adenoviral magnetofection can be a suitable method for increasing the efficacy of gene delivery into bone marrow stromal cell (BMSC) and for generation of a high level of bone morphogenic protein (BMP) secretion at a minimized viral titer. Materials and Methods: Primary BMSCs were isolated from C57BL6 mice and transduced with adenoviral vectors encoding ${\beta}$ galactosidase or BMP2 and BMP7. The level of BMP secretion, activity of osteoblast differentiation, and cell viability of magnetofection were measured and compared with those of the control group. Results: The expression level of ${\beta}$ galactosidase showed that the cell transduction efficiency of AdLacZ increased according to the increased amount of magnetic nanoparticles. No change in cell viability was observed after magnetofection with 2 ${\mu}L$ of magnetic nanoparticle. Secretion of BMP2 or BMP7 was accelerated after transduction of AdBMP2 and 7 with magnetofection. AdBMP2 adenoviral magnetofection resulted in up to 7.2-fold higher secretion of BMP2, compared with conventional AdBMP2-transduced BMSCs. Magnetofection also induced a dramatic increase in secretion of BMP7 by up to 10-fold compared to the control. Use of only 1 multiplicity of infection (moi) of magnetofection with adenoviral transduction of AdBMP2 or AdBMP7 resulted in significantly higher transgene expression compared to 20 moi of conventional adenoviral transduction. Conclusion: Magnetic particle-mediated gene transudation is a highly efficient method of gene delivery to BMSCs. Magnetofection can lower the amount of viral particles while improving the efficacy of gene delivery.

Keywords

References

  1. Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 2001;19:180-92. https://doi.org/10.1634/stemcells.19-3-180
  2. Scherer F, Anton M, Schillinger U, Henke J, Bergemann C, Krüger A, et al. Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther 2002;9:102-9. https://doi.org/10.1038/sj.gt.3301624
  3. Plank C, Scherer F, Schillinger U, Bergemann C, Anton M. Magnetofection: enhancing and targeting gene delivery with superparamagnetic nanoparticles and magnetic fields. J Liposome Res 2003;13:29-32. https://doi.org/10.1081/LPR-120017486
  4. Edgell CJ, Curiel DT, Hu PC, Marr HS. Efficient gene transfer to human endothelial cells using DNA complexed to adenovirus particles. Biotechniques 1998;25:264-8, 270-2.
  5. Tanner FC, Carr DP, Nabel GJ, Nabel EG. Transfection of human endothelial cells. Cardiovasc Res 1997;35:522-8. https://doi.org/10.1016/S0008-6363(97)00151-X
  6. Krötz F, de Wit C, Sohn HY, Zahler S, Gloe T, Pohl U, et al. Magnetofection--a highly efficient tool for antisense oligonucleotide delivery in vitro and in vivo. Mol Ther 2003;7:700-10. https://doi.org/10.1016/S1525-0016(03)00065-0
  7. Gazit D, Turgeman G, Kelley P, Wang E, Jalenak M, Zilberman Y, et al. Engineered pluripotent mesenchymal cells integrate and differentiate in regenerating bone: a novel cell-mediated gene therapy. J Gene Med 1999;1:121-33. https://doi.org/10.1002/(SICI)1521-2254(199903/04)1:2<121::AID-JGM26>3.0.CO;2-J
  8. Franceschi RT, Wang D, Krebsbach PH, Rutherford RB. Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7. J Cell Biochem 2000;78:476-86. https://doi.org/10.1002/1097-4644(20000901)78:3<476::AID-JCB12>3.0.CO;2-5
  9. Gottschalk S, Sparrow JT, Hauer J, Mims MP, Leland FE, Woo SL, et al. A novel DNA-peptide complex for efficient gene transfer and expression in mammalian cells. Gene Ther 1996;3:448-57.
  10. Haines AM, Irvine AS, Mountain A, Charlesworth J, Farrow NA, Husain RD, et al. CL22 - a novel cationic peptide for efficient transfection of mammalian cells. Gene Ther 2001;8:99-110. https://doi.org/10.1038/sj.gt.3301314
  11. Mehrara BJ, Saadeh PB, Steinbrech DS, Dudziak M, Spector JA, Greenwald JA, et al. Adenovirus-mediated gene therapy of osteoblasts in vitro and in vivo. J Bone Miner Res 1999;14:1290-301. https://doi.org/10.1359/jbmr.1999.14.8.1290
  12. Olmsted EA, Blum JS, Rill D, Yotnda P, Gugala Z, Lindsey RW, et al. Adenovirus-mediated BMP2 expression in human bone marrow stromal cells. J Cell Biochem 2001;82:11-21. https://doi.org/10.1002/jcb.1106
  13. Lieberman JR, Daluiski A, Stevenson S, Wu L, McAllister P, Lee YP, et al. The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats. J Bone Joint Surg Am 1999;81:905-17. https://doi.org/10.2106/00004623-199907000-00002
  14. Breitbart AS, Grande DA, Mason JM, Barcia M, James T, Grant RT. Gene-enhanced tissue engineering: applications for bone healing using cultured periosteal cells transduced retrovirally with the BMP-7 gene. Ann Plast Surg 1999;42:488-95. https://doi.org/10.1097/00000637-199905000-00005
  15. Verma IM, Somia N. Gene therapy-promises, problems and prospects. Nature 1997;389:239-42. https://doi.org/10.1038/38410
  16. Partridge K, Yang X, Clarke NM, Okubo Y, Bessho K, Sebald W, et al. Adenoviral BMP-2 gene transfer in mesenchymal stem cells: in vitro and in vivo bone formation on biodegradable polymer scaffolds. Biochem Biophys Res Commun 2002;292:144-52. https://doi.org/10.1006/bbrc.2002.6623
  17. Franceschi RT, Yang S, Rutherford RB, Krebsbach PH, Zhao M, Wang D. Gene therapy approaches for bone regeneration. Cells Tissues Organs 2004;176:95-108. https://doi.org/10.1159/000075031
  18. Russell WC. Update on adenovirus and its vectors. J Gen Virol 2000;81:2573-604. https://doi.org/10.1099/0022-1317-81-11-2573
  19. Zhao M, Zhao Z, Koh JT, Jin T, Franceschi RT. Combinatorial gene therapy for bone regeneration: cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2, 4, and 7. J Cell Biochem 2005;95:1-16. https://doi.org/10.1002/jcb.20411
  20. Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab 2003;80:148-58. https://doi.org/10.1016/j.ymgme.2003.08.016
  21. Reid T, Warren R, Kirn D. Intravascular adenoviral agents in cancer patients: lessons from clinical trials. Cancer Gene Ther 2002;9:979-86. https://doi.org/10.1038/sj.cgt.7700539
  22. Marshall E. Gene therapy death prompts review of adenovirus vector. Science 1999;286:2244-5. https://doi.org/10.1126/science.286.5448.2244
  23. Bergelson JM. Receptors mediating adenovirus attachment and internalization. Biochem Pharmacol 1999;57:975-9. https://doi.org/10.1016/S0006-2952(98)00332-3
  24. Hung SC, Lu CY, Shyue SK, Liu HC, Ho LL. Lineage diffe-rentiation-associated loss of adenoviral susceptibility and Coxsackie-adenovirus receptor expression in human mesenchymal stem cells. Stem Cells 2004;22:1321-9. https://doi.org/10.1634/stemcells.2003-0176
  25. Sapet C, Laurent N, de Chevigny A, Le Gourrierec L, Bertosio E, Zelphati O, et al. High transfection efficiency of neural stem cells with magnetofection. Biotechniques 2011;50:187-9.
  26. Sapet C, Pellegrino C, Laurent N, Sicard F, Zelphati O. Magnetic nanoparticles enhance adenovirus transduction in vitro and in vivo. Pharm Res 2012;29:1203-18. https://doi.org/10.1007/s11095-011-0629-9
  27. Veiseh O, Gunn JW, Zhang M. Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliv Rev 2010;62:284-304. https://doi.org/10.1016/j.addr.2009.11.002
  28. Plank C, Vlaskou D, Schillinger U, Mykhaylyk O. Magneto-fectionTM platform: from magnetic nanoparticles to novel nucleic acid therapeutics. Ther Deliv 2011;2:717-26. https://doi.org/10.4155/tde.11.37
  29. Zhang Y, Li W, Ou L, Wang W, Delyagina E, Lux C, et al. Targeted delivery of human VEGF gene via complexes of magnetic nanoparticle-adenoviral vectors enhanced cardiac regeneration. PLoS One 2012;7:e39490. https://doi.org/10.1371/journal.pone.0039490
  30. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-72. https://doi.org/10.1016/j.cell.2007.11.019
  31. Park HY, Noh EH, Chung HM, Kang MJ, Kim EY, Park SP. Efficient generation of virus-free iPS cells using liposomal magnetofection. PLoS One 2012;7:e45812. https://doi.org/10.1371/journal.pone.0045812

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