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Repair of bone defect by using vascular bundle implantation combined with Runx II gene-transfected adipose-derived stem cells and a biodegradable matrix

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Abstract

A large hurdle in orthopedics today is the difficulty of dealing with the non-union of fractured bones. We therefore evaluated the effects of runt-related transcription factor II (Runx II), a factor used to create gene-modified tissue-engineered bone, combined with vascular bundle implantation for repairing segmental bone defects. Adenovirus Runx II gene (Ad-Runx II)-modified rabbit adipose-derived stem cells (ADSCs) were seeded onto polylactic acid/polycaprolacton (PLA/PCL) scaffolds to construct gene-modified tissue-engineered bone. The following four methods were used for repair in rabbit radial-defect (1.5 cm long) models: gene-modified tissue-engineered bone with vascular bundle (Group A), gene-modified tissue-engineered bone (Group B), non-gene-modified tissue-engineered bone with vascular bundle (Group C), and PLA/PCL scaffolds only (Group D). X-ray, histological examination, biomechanics analysis, and micro-angiography were conducted 4, 8, and 12 weeks later to determine angiogenesis and osteogenesis. The volume and speed of production of newly formed bones in Group A were significantly superior to those in other groups, and de-novo vascular network circulation from the vessel bundle through newly formed bone tissue was observed, with the defect being completely repaired. Group B showed a slightly better effect in terms of speed and quality of bone formation than Group C, whereas the bone defect in Group D was replaced by fibrous tissue. The maximal anti-bending strength in Group A was significantly higher than that in the other groups. Runx II gene therapy combined with vascular bundle implantation thus displays excellent abilities for osteoinduction and vascularization and is a promising method for the treatment of bone non-union and defect.

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Abbreviations

Runx II:

Runt-related transcription factor II

Ad-Runx II:

Adenovirus Runx II gene

ADSCs:

Adipose-derived stem cells

PLA/PCL:

Polylactic acid/polycaprolacton

PBS:

Phosphate-buffered saline

VEGF:

Vascular endothelial growth factor

References

  • An C, Cheng Y, Yuan Q, Li J (2010) IGF-1 and BMP-2 induces differentiation of adipose-derived mesenchymal stem cells into chondrocytes-like cells. Ann Biomed Eng 38:1647–1654

    Article  PubMed  Google Scholar 

  • Beier JP, Horch RE, Hess A, Arkudas A, Heinrich J, Loew J et al (2010) Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model. J Tissue Eng Regen Med 4:216–223

    Article  PubMed  CAS  Google Scholar 

  • Carano RAD, Filvaroff EH (2003) Angiogenesis and bone repair. Drug Discov Today 8:980–989

    Article  PubMed  CAS  Google Scholar 

  • Dai KR, Xu XL, Tang TT, Zhu ZA, Yu CF, Lou JR et al (2005) Repairing of goat tibial bone defects with BMP-2 gene-modified tissue-engineered bone. Calcif Tissue Int 77:55–61

    Article  PubMed  CAS  Google Scholar 

  • Divakov MG (1991) Revascularization of avascular spongy bone and head of the femur in transplantation of vascular bundle (an experimental and clinical study). Acta Chir Plast 33:114–125

    PubMed  CAS  Google Scholar 

  • Dragoo JL, Samimi B, Zhu M, Hame SL, Thomas BJ, Lieberman JR et al (2003) Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads. J Bone Joint Surg Br 85:740–747

    PubMed  CAS  Google Scholar 

  • Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754

    Article  PubMed  CAS  Google Scholar 

  • Eweida AM, Nabawi AS, Elhammady HA, Marei MK, Khalil MR, Shawky MS et al (2012) Axially vascularized bone substitutes: a systematic review of literature and presentation of a novel model. Arch Orthop Trauma Surg 132:1353–1362

    Article  PubMed  CAS  Google Scholar 

  • Follmar KE, Prichard HL, DeCroos FC, Wang HT, Levin LS, Klitzman B et al (2007) Combined bone allograft and adipose-derived stem cell autograft in a rabbit model. Ann Plast Surg 58:561–565

    Article  PubMed  CAS  Google Scholar 

  • Fröhlich M, Grayson WL, Wan LQ, Marolt D, Drobnic M, Vunjak-Novakovic G et al (2008) Tissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. Curr Stem Cell Res Ther 3:254–264

    Article  PubMed  Google Scholar 

  • Justesen J, Pedersen SB, Stenderup K, Kassem M (2004) Subcutaneous adipocytes can differentiate into bone-forming cells in vitro and in vivo. Tissue Eng 10:381–391

    Article  PubMed  CAS  Google Scholar 

  • Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y et al (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764

    Article  PubMed  CAS  Google Scholar 

  • Kruyt MC, De Bruijn J, Veenhof M, Oner FC, Van Blitterswijk CA, Verbout AJ, Dhert WJ (2003) Application and limitations of chloromethyl-benzamidodialkylcarbocyanine for tracing cells used in bone tissue engineering. Tissue Eng 9:105–115

    Article  PubMed  CAS  Google Scholar 

  • Laschke MW, Harder Y, Amon M, Martin I, Farhadi J, Ring A et al (2006) Angiogenesis in tissue engineering:breathing life into constructed tissue substitutes. Tissue Eng 12:2093–2104

    Article  PubMed  CAS  Google Scholar 

  • Li J, Zhao Q, Wang E, Zhang C, Wang G, Yuan Q (2012) Dynamic compression of rabbit adipose-derived stem cells transfected with insulin-like growth factor 1 in chitosan/gelatin scaffolds induces chondrogenesis and matrix biosynthesis. J Cell Physiol 227:2003–2012

    Article  PubMed  CAS  Google Scholar 

  • Miranville A, Heeschen C, Sengenès C, Curat CA, Busse R, Bouloumié A (2004) Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110:349–355

    Article  PubMed  CAS  Google Scholar 

  • Mizuno H, Zuk PA, Zhu M, Lorenz HP, Benhaim P, Hedrick MH (2002) Myogenic differentiation by human processed lipoaspirate cells. Plast Reconstr Surg 109:199–209

    Article  PubMed  Google Scholar 

  • Nakasa T, Ishida O, Sunagawa T, Nakamae A, Yasunaga Y, Agung M et al (2005) Prefabrication of vascularized bone graft using a combination of fibroblast growth factor-2 and vascular bundle implantation into a novel interconnected porous calcium hydroxyapatite ceramic. J Biomed Mater Res A 75:350–355

    PubMed  Google Scholar 

  • Nguyen LH, Annabi N, Nikkhah M, Bae H, Binan L, Park S, Kang Y, Yang Y, Khademhosseini A (2012) Vascularized bone tissue engineering: approaches for potential improvement. Tissue Eng Part B Rev 18:363–382

    Article  PubMed  CAS  Google Scholar 

  • Nikolić DK, Jovanović Z, Turković G, Vulović R, Mladenović M (2002) Supracondylar missile fractures of the femur. Injury 33:161–166

    Article  PubMed  Google Scholar 

  • Ozyurek A, Leblebicioglu G, Bilgili H, Kurum B, Gedikoglu G, Atasever T et al (2008) Effects of vascular bundle implantation on autograft, fresh-frozen allograft, and xenograft incorporation in a rabbit model. Orthopedics 31:135

    Article  PubMed  Google Scholar 

  • Rodriguez AM, Elabd C, Amri EZ, Ailhaud G, Dani C (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    Article  Google Scholar 

  • Safak T, Akyürek M, Ozcan G, Keçik A, Aydin M (2000) Osteocutaneous flap prefabrication based on the principle of vascular induction: an experimental and clinical study. Plast Reconstr Surg 105:1304–1313

    PubMed  CAS  Google Scholar 

  • Winter A, Breit S, Parsch D, Benz K, Steck E, Hauner H et al (2003) Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells. Arthritis Rheum 48:418–429

    Article  PubMed  CAS  Google Scholar 

  • Yang M, Ma QJ, Dang GT, Ma K, Chen P, Zhou CY (2005) In vitro and in vivo induction of bone formation based on ex vivo gene therapy using rat adipose-derived adult stem cells expressing BMP-7. Cytotherapy 7:273–281

    Article  PubMed  CAS  Google Scholar 

  • Zelzer E, Glotzer DJ, Hartmann C, Thomas D, Fukai N, Soker S et al (2001) Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2. Mech Dev 106:97–106

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Yang M, Lin L, Chen P, Ma KT, Zhou CY et al (2006) Runx2 overexpression enhances osteoblastic differentiation and mineralization in adipose–derived stem cells in vitro and in vivo. Calcif Tissue Int 79:169–178

    Article  PubMed  CAS  Google Scholar 

  • Zhao M, Zhou J, Li X, Fang T, Dai W, Yin W, Dong J (2011) Repair of bone defect with vascularized tissue engineered bone graft seeded with mesenchymal stem cells in rabbits. Microsurgery 31:130–137

    Article  PubMed  CAS  Google Scholar 

  • Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Ninth People’s Hospital, Medical School of Shanghai, Jiao Tong University, Shanghai, People’s Republic of China

    Dong Han

  2. Department of Orthopedics, Shengjing Hospital of China Medical University, No.36, Sanhao Street, Heping District, Shenyang, 110004, People’s Republic of China

    Jianjun Li

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  1. Dong Han
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  2. Jianjun Li
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Correspondence to Jianjun Li.

Additional information

This work was supported by a grant from the National Natural Science Foundation of China (no. 30772216).

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Han, D., Li, J. Repair of bone defect by using vascular bundle implantation combined with Runx II gene-transfected adipose-derived stem cells and a biodegradable matrix. Cell Tissue Res 352, 561–571 (2013). https://doi.org/10.1007/s00441-013-1595-9

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