Quantitative, structural, and image-based mechanical analysis of nonunion fracture repaired by genetically engineered mesenchymal stem cells

JOURNAL OF BIOMECHANICS

卷:43

Article

Kallai, Ilan¹  van Lenthe, G. Harry^2,3  Ruffoni, Davide²  Zilberman, Yoram¹  Muller, Ralph²  Pelled, Gadi^1,4,5  Gazit, Dan^1,4,5 

[1] Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Skeletal Biotech Lab, IL-91120 Jerusalem, Israel

[2] ETH, Inst Biomech, Zurich, Switzerland

[3] Katholieke Univ Leuven, Div Biomech, Leuven, Belgium

[4] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA

[5] Cedars Sinai Med Ctr, Cedars Sinai Regenerat Med Inst CS RMI, Los Angeles, CA 90048 USA

关键词: Micro-finite element model;    Micro-computed tomography;    Bone tissue regeneration;    Mesenchymal stem cells;   

DOI  :  10.1016/j.jbiomech.2010.04.031

来源: Elsevier

【 摘 要 】

Stem cell-mediated gene therapy for fracture repair, utilizes genetically engineered mesenchymal stem cells (MSCs) for the induction of bone growth and is considered a promising approach in skeletal tissue regeneration. Previous studies have shown that murine nonunion fractures can be repaired by implanting MSCs over-expressing recombinant human bone morphogenetic protein-2 (rhBMP-2). Nanoindentation studies of bone tissue induced by MSCs in a radius fracture site indicated similar elastic modulus compared to intact murine bone, eight weeks post-treatment. In the present study we sought to investigate temporal changes in microarchitecture and biomechanical properties of repaired murine radius bones, following the implantation of MSCs. High-resolution micro-computed tomography (micro-CT) was performed 10 and 35 weeks post MSC implantation, followed by micro-finite element (micro-FE) analysis. The results have shown that the regenerated bone tissue remodels over time, as indicated by a significant decrease in bone volume, total volume, and connectivity density combined with an increase in mineral density. In addition, the axial stiffness of limbs repaired with MSCs was 2-1.5 times higher compared to the contralateral intact limbs, at 10 and 35 weeks post-treatment. These results could be attributed to the fusion that occurred in between the ulna and radius bones. In conclusion, although MSCs induce bone formation, which exceeds the fracture site, significant remodeling of the repair callus occurs over time. In addition, limbs treated with an MSC graft demonstrated superior biomechanical properties, which could indicate the clinical benefit of future MSC application in nonunion fracture repair. (C) 2010 Elsevier Ltd. All rights reserved.

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