The effect of mesenchymal stem cell sheets on structural allograft healing of critical sized femoral defects in mice

• Published in: Biomaterials Vol. 35; no. 9; pp. 2752 - 2759
• Main Authors: Long, Teng, Zhu, Zhenan, Awad, Hani A, Schwarz, Edward M, Hilton, Matthew J, Dong, Yufeng
• Format: Journal Article
• Language: English
• Published: Netherlands 01-03-2014
• Subjects: Advanced Basic Science; Allografts; Animals; Biomechanical Phenomena; Cartilage - growth & development; Cell Separation; Cells, Cultured; Dentistry; Femur - pathology; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mice; Mice, Inbred C57BL; Osseointegration; Osteogenesis; Torsion, Mechanical; Wound Healing; Cell sheet; Bone tissue engineering; Bone marrow stem cell; Bone allograft
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.12.039

Abstract Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue-engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo , allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of X-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing.