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Vet Comp Orthop Traumatol 2011; 24(02): 113-121
DOI: 10.3415/VCOT-10-03-0046
Original Research
Schattauer GmbH

The efficacy of allogeneic mesenchymal precursor cells for the repair of an ovine tibial segmental defect

J. R. Field
1   CORe: Comparative Orthopaedic Research Surgical Facility, School of Medicine, Flinders University, Bedford Park, South Australia, Australia
,
M. McGee
2   Department of Orthopaedics and Trauma, Royal Adelaide Hospital and University of Adelaide, South Australia, Australia
,
R. Stanley
1   CORe: Comparative Orthopaedic Research Surgical Facility, School of Medicine, Flinders University, Bedford Park, South Australia, Australia
,
G. Ruthenbeck
1   CORe: Comparative Orthopaedic Research Surgical Facility, School of Medicine, Flinders University, Bedford Park, South Australia, Australia
,
T. Papadimitrakis
3   Mesoblast Pty. Ltd., Melbourne, Australia
,
A. Zannettino
4   Institute of Medical and Veterinary Science, University of Adelaide, South Australia, Australia
,
S. Gronthos
4   Institute of Medical and Veterinary Science, University of Adelaide, South Australia, Australia
,
S. Itescu
3   Mesoblast Pty. Ltd., Melbourne, Australia
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 23. März 2010

Accepted: 05. Januar 2010

Publikationsdatum:
19. Dezember 2017 (online)

Auch verfügbar auf
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Summary

Introduction: Synthetic void-fillers offer an alternative to autograft or allograft bone in the repair of segmental defects. However, the reparative process is delayed as only osteo-conductive elements are present. The inclusion of pluripotential cells may resolve this limitation, and the use of allogeneic tissue provides the opportunity for an off-the-shelf remedy. The current study evaluated the utilisation of mesenchymal precursor cells (MPC) for the repair of an ovine critical-size tibial segmental defect.

Methods: Twenty-four, mature female sheep underwent surgery for the creation of a 3 cm tibial diaphyseal defect. In one group of 12 sheep the scaffold was used alone, and in the second group the scaffold was seeded with MPC. The defect was stabilised using a locking intramedullary nail and allowed to heal over a nine-month-period. Outcome assessments of healing included radiology of callus formation, computed tomography, assessment of new-bone volume, mechanical attributes, and histological evaluation of linear bone apposition rate and tissue response.

Results: The MPC-treated group displayed a significantly greater level of callus formation and rate of bone apposition in the defect.

Discussion: The incorporation of allogeneic MPC to a synthetic void filler stimulated early repair of critical-size diaphyseal segmental defects and holds potential as an off-the-shelf therapy for augmenting bone regeneration.

Keywords

Mesenchymal precursor cells - tibial segmental defect - ovine model - trauma
 

  • References

  • 1 Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury 2005; 36 (Suppl. 03) S20-S27.
    PubMedSuche in Google Scholar
  • 2 Betz RR. Limitations of autograft and allograft: new synthetic solutions. Orthopedics 2002; 25: S561-S570.
    PubMedSuche in Google Scholar
  • 3 Boyce T, Edwards J, Scarborough N. Allograft bone. The influence of processing on safety and performance. Orthop Clin North Am 1999; 30: 571-581.
    CrossrefPubMedSuche in Google Scholar
  • 4 Field JR, McGee M, Wildenaur C. et al. The utilization of a synthetic bone void filler in the repair of a femoral segmental defect. Vet Comp Orthop Traumatol 2009; 22: 87-95.
    Thieme ConnectPubMedSuche in Google Scholar
  • 5 Giannoni P, Mastrogiacomo M, Alini M. et al. Regeneration of large bone defects in sheep using bone marrow stromal cells. J Tissue Eng Regen Med 2008; 2: 253-262.
    CrossrefPubMedSuche in Google Scholar
  • 6 Cancedda R, Giannoni P, Mastrogiacomo M. A tissue engineering approach to bone repair in large animal models and in clinical practice. Biomaterials 2007; 28: 4240-4250.
    CrossrefPubMedSuche in Google Scholar
  • 7 Sarkar MR, Augat P, Shefelbine SJ. et al. Bone formation in a long bone defect model using a platelet-rich plasma-loaded collagen scaffold. Bio-materials 2006; 27: 1817-1823.
    CrossrefPubMedSuche in Google Scholar
  • 8 Krebsbach PH, Mankani MH, Satomura K. et al. Repair of craniotomy defects using bone marrow stromal cells. Transplantation 1998; 66: 1272-1278.
    CrossrefPubMedSuche in Google Scholar
  • 9 Bruder SP, Kurth A, Shea M. et al. Bone regeneration by implantation of purifed, culture-expanded, human mesenchymal stems cells. J Orthop Res 1998; 16: 155-162.
    CrossrefPubMedSuche in Google Scholar
  • 10 Chistolini P, Ruspantini I, Bianco P. et al. Bio-mechanical evaluation of cell-loaded and cell-free hydroxyapatite implants for the reconstruction of segmental bone defects. J Mater Sci Mater Med 1999; 10: 739-742.
    CrossrefPubMedSuche in Google Scholar
  • 11 Petite H, Viateau V, Bensaid W. et al. Tissue-engineered bone regeneration. Nat Biotechnol 2000; 18: 959-963.
    CrossrefPubMedSuche in Google Scholar
  • 12 Kon E, Muraglia A, Corsi A. et al. Autologous bone marrow stromal cells loaded onto porous hydro-xyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res 2000; 49: 328-337.
    CrossrefPubMedSuche in Google Scholar
  • 13 Shang Q, Wang Z, Liu W. et al. Tissue-engineered bone repair of sheep cranial defects with auto-logous bone marrow stromal cells. J Craniofac Surg 2001; 12: 586-593 discussion 594-585.
    CrossrefPubMedSuche in Google Scholar
  • 14 Gronthos S, Zannettino AC, Hay SJ. et al. Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J Cell Sci 2003; 116: 1827-1835.
    CrossrefPubMedSuche in Google Scholar
  • 15 Gronthos S, Zanettino AC. The potential of marrow stromal stem cells to repair bone defects and fractures. J Stem Cells 2006; 1: 35-45.
    PubMedSuche in Google Scholar
  • 16 Gronthos S, Fitter S, Diamond P. et al. A novel monoclonal antibody (STRO-3) identifies an iso-form of tissue nonspecific alkaline phosphatase expressed by multipotent bone marrow stromal stem cells. Stem Cells Dev 2007; 16: 953-963.
    CrossrefPubMedSuche in Google Scholar
  • 17 Hamamoto H, Gorman JH, Ryan LP. 3rd et al. Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage. Ann Thorac Surg 2009; 87: 794-801.
    CrossrefPubMedSuche in Google Scholar
  • 18 Lazarus HM, Koc ON, Devine SM, et al.. Cotrans-plantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 2005; 11: 389-398.
    CrossrefPubMedSuche in Google Scholar
  • 19 Chung NG, Jeong DC, Park SJ. et al. Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex mismatched murine hematopoietic stem cell transplantation. Int J Hematol 2004; 80: 370-376.
    CrossrefPubMedSuche in Google Scholar
  • 20 Maitra B, Szekely E, Gjini K, et al.. Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant 2004; 33: 597-604.
    CrossrefPubMedSuche in Google Scholar
  • 21 McCarty RC, Gronthos S, Zannettino AC, et al.. Characterisation and developmental potential of ovine bone marrow derived mesenchymal stem cells. J Cell Physiol 2009; 219: 324-333.
    CrossrefPubMedSuche in Google Scholar
  • 22 Gronthos S, McCarty R, Mrozik K, et al.. Heat shock protein-90 beta is expressed at the surface of multipotential mesenchymal precursor cells: generation of a novel monoclonal antibody, STRO-4, with specificity for mesenchymal precursor cells from human and ovine tissues. Stem Cells Dev 2009; 18: 1253-1262.
    CrossrefPubMedSuche in Google Scholar
  • 23 Erben RG.. Bone labelling techniques. In: An YH, Martin KL. editors Handbook of histology methods for bone and cartilage New Jersey: Humana Press; 2003: 99-118.
    Suche in Google Scholar
  • 24 Pautke C, Tischer T, Vogt S, et al.. New advances in fluorochrome sequential labelling of teeth using seven different fluorochromes and spectral image analysis. J Anat 2007; 210: 117-121.
    CrossrefPubMedSuche in Google Scholar
  • 25 Mankin HJ. Orthopaedics in, 2013; a prospection. J Bone Joint Surg Am 1983; 65: 1190-1194.
    CrossrefPubMedSuche in Google Scholar
  • 26 Kraus KH, Kirker-Head C. Mesenchymal stem cells and bone regeneration. Vet Surg 2006; 35: 232-242.
    CrossrefPubMedSuche in Google Scholar
  • 27 Arinzeh TL, Peter SJ, Archambault MP. et al. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am 2003; 85: 1927-1935.
    CrossrefPubMedSuche in Google Scholar
  • 28 Viateau V, Guillemin G, Bousson V. et al. Long-bone critical-sized defects treated with tissue-engineered grafts: a study on sheep. J Orthop Res 2007; 25: 741-749.
    CrossrefPubMedSuche in Google Scholar
  • 29 Maissen O, Eckhardt C, Gogolewski S. et al. Mechanical and radiological assessment of the influence of rhTGFß-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study. J Orthop Res 2006; 24: 1670-1678.
    CrossrefPubMedSuche in Google Scholar
  • 30 Gerhart TN, Kirker-Head CA, Kriz MJ. et al. Healing segmental femoral defects in sheep using recombinant human bone morphogenic protein. Clin Orthop Rel Res 1993; 293: 317-326.
    PubMedSuche in Google Scholar
  • 31 Pluhar GE, Turner AS, Pierce AR. et al. A comparison of two biomaterial carriers for osteogenic protein-1 (BMP-7) in an ovine critical defect model. J Bone Joint Surg. 2006; 88: 960-966.
    PubMedSuche in Google Scholar
  • 32 Marcacci M, Kon E, Zaffagnini S. et al. Reconstruction of extensive long-bone defects in sheep using porous hydroxyapatite sponges. Calcif Tissue Int 1999; 64: 83-90.
    CrossrefPubMedSuche in Google Scholar
  • 33 Nasef A, Zhang YZ, Mazurier C. et al. Selected Stro-1–enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation. Int J Lab Hematol 2009; 31: 9-19.
    CrossrefPubMedSuche in Google Scholar