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

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 osteoconductive 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.

[1]  K. Mrozik,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. , 2009, Stem cells and development.

[2]  S. Gronthos,et al.  Characterisation and developmental potential of ovine bone marrow derived mesenchymal stem cells , 2009, Journal of cellular physiology.

[3]  J. Gorman,et al.  Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage. , 2009, The Annals of thoracic surgery.

[4]  L. Fouillard,et al.  Selected Stro‐1‐enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation , 2009, International journal of laboratory hematology.

[5]  M. Mastrogiacomo,et al.  Regeneration of large bone defects in sheep using bone marrow stromal cells , 2008, Journal of tissue engineering and regenerative medicine.

[6]  A. Zannettino,et al.  A novel monoclonal antibody (STRO-3) identifies an isoform of tissue nonspecific alkaline phosphatase expressed by multipotent bone marrow stromal stem cells. , 2007, Stem cells and development.

[7]  Paolo Giannoni,et al.  A tissue engineering approach to bone repair in large animal models and in clinical practice. , 2007, Biomaterials.

[8]  V. Bousson,et al.  Long‐bone critical‐size defects treated with tissue‐engineered grafts: A study on sheep , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[9]  M. Schieker,et al.  New advances in fluorochrome sequential labelling of teeth using seven different fluorochromes and spectral image analysis , 2007, Journal of anatomy.

[10]  S. Gogolewski,et al.  Mechanical and radiological assessment of the influence of rhTGFβ‐3 on bone regeneration in a segmental defect in the ovine tibia: Pilot study , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  D L Wheeler,et al.  A comparison of two biomaterial carriers for osteogenic protein-1 (BMP-7) in an ovine critical defect model. , 2006, The Journal of bone and joint surgery. British volume.

[12]  K. Kraus,et al.  Mesenchymal stem cells and bone regeneration. , 2006, Veterinary surgery : VS.

[13]  L. Claes,et al.  Bone formation in a long bone defect model using a platelet-rich plasma-loaded collagen scaffold. , 2006, Biomaterials.

[14]  Eleftherios Tsiridis,et al.  Bone substitutes: an update. , 2005, Injury.

[15]  Andrea Bacigalupo,et al.  Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[16]  Soo-Jeong Park,et al.  Cotransplantation of Marrow Stromal Cells May Prevent Lethal Graft-versus-Host Disease in Major Histocompatibility Complex Mismatched Murine Hematopoietic Stem Cell Transplantation , 2004, International journal of hematology.

[17]  S. Haynesworth,et al.  Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation , 2004, Bone Marrow Transplantation.

[18]  K. Kraus,et al.  Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. , 2003, The Journal of bone and joint surgery. American volume.

[19]  S. Gronthos,et al.  Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow , 2003, Journal of Cell Science.

[20]  R. Betz,et al.  Limitations of autograft and allograft: new synthetic solutions. , 2002, Orthopedics.

[21]  Q. Shang,et al.  Tissue-Engineered Bone Repair of Sheep Cranial Defects with Autologous Bone Marrow Stromal Cells , 2001, The Journal of craniofacial surgery.

[22]  A. Meunier,et al.  Tissue-engineered bone regeneration , 2000, Nature Biotechnology.

[23]  A Boyde,et al.  Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. , 2000, Journal of biomedical materials research.

[24]  P. Chistolini,et al.  Biomechanical evaluation of cell-loaded and cell-free hydroxyapatite implants for the reconstruction of segmental bone defects , 1999, Journal of materials science. Materials in medicine.

[25]  N. Scarborough,et al.  Allograft bone. The influence of processing on safety and performance. , 1999, The Orthopedic clinics of North America.

[26]  K. Satomura,et al.  Repair of craniotomy defects using bone marrow stromal cells. , 1998, Transplantation.

[27]  W. Hayes,et al.  Bone regeneration by implantation of purified, culture‐expanded human mesenchymal stem cells , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[28]  H. Mankin‡ Orthopaedics in 2013: a prospection. , 1983, The Journal of bone and joint surgery. American volume.

[29]  S. Gronthos,et al.  The efficacy of allogeneic mesenchymal precursor cells for the repair of an ovine tibial segmental defect , 2011, Veterinary and Comparative Orthopaedics and Traumatology.

[30]  A. Kurmis,et al.  The utilization of a synthetic bone void filler (JAX) in the repair of a femoral segmental defect , 2009, Veterinary and Comparative Orthopaedics and Traumatology.