Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical sized segmental tibial bone defects in aged sheep

Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
Acta biomaterialia (Impact Factor: 5.68). 04/2013; 9(8). DOI: 10.1016/j.actbio.2013.04.035
Source: PubMed

ABSTRACT Mesenchymal progenitor cells (MPCs) represent an attractive cell population for bone tissue engineering. Their special immunological characteristics suggest that MPCs may be used in an allogenic application. The objective of this study was to compare the regenerative potential of autologous vs. allogenic MPCs in an ovine critical-sized segmental defect model. Ovine MPCs were isolated from bone marrow aspirates, expanded and cultured with osteogenic media for two weeks before implantation. Autologous and allogenic transplantation was performed by using the cell-seeded scaffolds, unloaded scaffolds and the application of autologous bone grafts served as control groups (n=6). Bone healing was assessed twelve weeks after surgery by radiology, micro computed tomography, biomechanical testing and histology. Radiology, biomechanical testing and histology revealed no significant difference in bone formation between the autologous and allogenic group. Both cell groups showed more bone formation than the scaffold alone, whereas the biomechanical data showed no significant differences between the cell-groups and the unloaded scaffolds. The results of the study suggest that scaffold based bone tissue engineering using allogenic cells offers the potential for an off the shelf product. Therefore, the results of this study serve as an important baseline for the translation of the assessed concepts into clinical application.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we compared the efficiency of osteoblast differentiation media (ODM) containing three distinct reagent combinations in osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) in monolayer culture. In addition, we analyzed growth and differentiation of hBMSCs on silk scaffolds and examined the bone-forming activity of a nanofibrous silk scaffold in a tibia diaphysis defect model of a rat hind limb with intramedullary nailing. Although all three ODM increased alkaline phosphatase activity to a comparable extent, the ODM containing bone morphogenetic protein-2 (BMP-2) was found to be significantly less effective in promoting mineral deposition than the others. Growth of hBMSCs on sponge-form silk scaffolds was faster than on nanofibrous ones, while osteoblastic differentiation was apparent in the cells grown on either type of scaffold. By contrast, bone formation was observed only at the edge of the nanofibrous scaffold implanted in the tibia diaphysis defect, suggesting that use of the silk scaffold alone is not sufficient for the reconstitution of the long bone defect. Since silk scaffolds can support cell growth and differentiation in vitro, loading MSCs on scaffolds might be necessary to improve the bone-forming activity of the scaffold in the long bone defect model.
    12/2013; 27(2). DOI:10.7852/ijie.2013.27.2.303
  • [Show abstract] [Hide abstract]
    ABSTRACT: Compromised bone-regenerating capability following a long bone fracture is often the result of reduced host bone marrow (BM) progenitor cell numbers and efficacy. Without surgical intervention, these malunions result in mobility restrictions, deformities, and disability. The clinical application of BM-derived mesenchymal stem cells (MSCs) is a feasible, minimally invasive therapeutic option to treat non-union fractures. This review focuses on novel, newly identified cell surface markers in both the mouse and human enabling the isolation and purification of osteogenic progenitor cells as well as their direct and indirect contributions to fracture repair upon administration. Furthermore, clinical success to date is summarized with commentary on autologous versus allogeneic cell sources and the methodology of cell administration. Given our clinical success to date in combination with recent advances in the identification, isolation, and mechanism of action of MSCs, there is a significant opportunity to develop improved technologies for defining therapeutic MSCs and potential to critically inform future clinical strategies for MSC-based bone regeneration.
    Stem Cell Research & Therapy 04/2014; 5(2):51. DOI:10.1186/scrt439 · 4.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the last few years, numerous new treatment methods have been developed for musculoskeletal diseases. Some of these new methods are based on the targeted use of stem cells to initiate healing processes, to compensate for deficits or to activate the regeneration of tendons, muscles, bones and cartilage. This goal can be achieved through the direct use of stem cells on or in a carrier material or through a combination with tissue engineering. In this article, we give a short overview of the possible fields of application of inducible pluripotent haematopoietic, and adult stem cells as well as on their use in musculoskeletal tissue. Furthermore, we provide a summary of the current legal situation concerning the application of stem cells in humans.
    Zeitschrift fur Orthopadie und Unfallchirurgie 08/2014; 152(4):320-327. DOI:10.1055/s-0034-1382867 · 0.62 Impact Factor


Available from
May 20, 2014