Bridging the gap: Bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects

Although autologous bone grafting represents an effective tool to induce osteogenic regeneration in local bone defects or pseudarthroses, it is associated with significant donor site morbidity and limited by the amount available for grafting. We investigate the potency of bone marrow aspiration concentrate (BMAC) to augment bone grafting and support bone healing. The functional and radiographic outcome of 39 patients with volumetric bone deficiencies treated with BMAC are presented and evaluated in a prospective clinical trial. A collagen sponge (Col) served as scaffold in 12 patients and a bovine hydroxyapatite (HA) was applied in the other 27 individuals. The minimal follow‐up was 6 months. Clinical and radiographic findings were completed by in vitro data. All patients showed new bone formation in radiographs during follow‐up. However, two patients underwent revision surgery due to a lack in bone healing. In contrast to the Col group, the postoperative bone formation appeared earlier in the HA group (HA group: 6.8 weeks vs. Col group 13.6 weeks). Complete bone healing was achieved in the HA group after 17.3 weeks compared to 22.4 weeks in the Col group. The average concentration factor of BMAC was 5.2 (SD 1.3). Flow cytometry confirmed the mesenchymal nature of the cells. Cells from BMAC created earlier and larger colonies of forming units fibroblasts (CFU‐F) compared to cells from bone marrow aspirate. BMAC combined with HA can reduce the time needed for healing of bone defects when compared to BMAC in combination with collagen sponge. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:173–180, 2011

[1]  R. Kolvenbach,et al.  Intraoperative adjunctive stem cell treatment in patients with critical limb ischemia using a novel point-of-care device. , 2010, Annals of vascular surgery.

[2]  M. Jäger,et al.  Zelltherapie bei Knochenheilungsstörungen , 2010, Der Orthopäde.

[3]  M. Nagata,et al.  Influence of the ratio of particulate autogenous bone graft/platelet‐rich plasma on bone healing in critical‐size defects: A histologic and histometric study in rat calvaria , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[4]  A. Mantalaris,et al.  Investigating the role of PDGF as a potential drug therapy in bone formation and fracture healing , 2009, Expert opinion on investigational drugs.

[5]  A. W. Wagoner Johnson,et al.  The influence of micropore size on the mechanical properties of bulk hydroxyapatite and hydroxyapatite scaffolds. , 2009, Journal of the mechanical behavior of biomedical materials.

[6]  N. Ishiguro,et al.  Differential Effects of Culture-expanded Bone Marrow Cells on the Regeneration of Bone Between the Femoral and the Tibial Lengthenings , 2009, Journal of pediatric orthopedics.

[7]  M. Nagata,et al.  Influence of the proportion of particulate autogenous bone graft/platelet-rich plasma on bone healing in critical-size defects: an immunohistochemical analysis in rat calvaria. , 2009, Bone.

[8]  J. R. Parsons,et al.  Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[9]  Nicole Falkensammer,et al.  Modified iliac bone harvesting--morbidity and patients' experience. , 2009, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[10]  Y. Verma,et al.  Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine , 2009, Journal of cellular and molecular medicine.

[11]  F. Schwarz,et al.  Surface- and nonsurface-dependent in vitro effects of bone substitutes on cell viability , 2009, Clinical Oral Investigations.

[12]  R. Ratei,et al.  Autologous Bone Marrow Cell Transplantation Increases Leg Perfusion and Reduces Amputations in Patients with Advanced Critical Limb Ischemia Due to Peripheral Artery Disease , 2009, Cell transplantation.

[13]  Stan Gronthos,et al.  The therapeutic applications of multipotential mesenchymal/stromal stem cells in skeletal tissue repair , 2009, Journal of cellular physiology.

[14]  M. Gelinsky,et al.  Bone formation in trabecular bone cell seeded scaffolds used for reconstruction of the rat mandible. , 2009, International Journal of Oral & Maxillofacial Surgery.

[15]  Attila Tárnok,et al.  Cellular diagnostics : basic principles, methods and clinical applications of flow cytometry , 2008 .

[16]  B. Liesenfeld,et al.  Design and rationale of a randomized, double-blind, placebo-controlled phase III study for autologous bone marrow cell transplantation in critical limb ischemia: the BONe Marrow Outcomes Trial in Critical Limb Ischemia (BONMOT-CLI). , 2008, VASA. Zeitschrift fur Gefasskrankheiten.

[17]  P. Kasten,et al.  The effect of platelet-rich plasma on healing in critical-size long-bone defects. , 2008, Biomaterials.

[18]  N. Ghodadra,et al.  Recombinant human bone morphogenetic protein-2 in the treatment of bone fractures , 2008, Biologics : targets & therapy.

[19]  M. Albitar,et al.  Toward the Identification of Mesenchymal Stem Cells in Bone Marrow and Peripheral Blood for Bone Regeneration , 2008, Implant dentistry.

[20]  P. Kasten,et al.  Effect of Platelet-rich Plasma on the in vitro Proliferation and Osteogenic Differentiation of Human Mesenchymal Stem Cells on Distinct Calcium Phosphate Scaffolds: The Specific Surface Area Makes a Difference , 2008, Journal of biomaterials applications.

[21]  M. Casal,et al.  Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery) , 2008, Journal of tissue engineering and regenerative medicine.

[22]  S. Lynch,et al.  Recombinant human platelet-derived growth factor: biology and clinical applications. , 2008, The Journal of bone and joint surgery. American volume.

[23]  D. Smiler,et al.  Bone Block Allograft Impregnated With Bone Marrow Aspirate , 2007, Implant dentistry.

[24]  V. Falanga,et al.  Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. , 2007, Tissue engineering.

[25]  E. Carlson,et al.  Effects of platelet-rich plasma at the cellular level on healing of autologous bone-grafted mandibular defects in dogs. , 2007, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[26]  R. Kolvenbach,et al.  Stem cell use in critical limb ischemia. , 2007, The Journal of cardiovascular surgery.

[27]  R. Todhunter,et al.  Use of a centrifugation-based, point-of-care device for production of canine autologous bone marrow and platelet concentrates. , 2006, American journal of veterinary research.

[28]  P. Hernigou,et al.  Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique. , 2006, The Journal of bone and joint surgery. American volume.

[29]  S. Ivanovski,et al.  The in vitro effect of different PRP concentrations on osteoblasts and fibroblasts. , 2006, Clinical oral implants research.

[30]  M. Jäger,et al.  Extensive H(+) release by bone substitutes affects biocompatibility in vitro testing. , 2006, Journal of biomedical materials research. Part A.

[31]  P. Giannoudis,et al.  Clinical applications of BMP-7: the UK perspective. , 2005, Injury.

[32]  T. Feser,et al.  Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells Cultured onto Three Different Polymers In Vitro , 2005, Annals of Biomedical Engineering.

[33]  F Beaujean,et al.  Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. , 2005, The Journal of bone and joint surgery. American volume.

[34]  C. Moser,et al.  Milieu-Adopted in vitro and in vivo Differentiation of Mesenchymal Tissues Derived from Different Adult Human CD34-Negative Progenitor Cell Clones , 2005, Cells Tissues Organs.

[35]  H. Zwipp,et al.  Osteocalcin enhances bone remodeling around hydroxyapatite/collagen composites. , 2005, Journal of biomedical materials research. Part A.

[36]  R. Taichman.  Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. , 2005, Blood.

[37]  N. Ishiguro,et al.  Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases. , 2004, Bone.

[38]  H. Tal,et al.  Efficacy of porous bovine bone mineral in various types of osseous deficiencies: clinical observations and literature review. , 2001, The International journal of periodontics & restorative dentistry.

[39]  C. Boehm,et al.  Age‐ and gender‐related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[40]  Y. Açil,et al.  Three-dimensional cultivation of human osteoblast-like cells on highly porous natural bone mineral. , 2000, Journal of biomedical materials research.

[41]  C. Joyner,et al.  Clonal analysis in vitro of osteogenic differentiation of marrow CFU-F. , 1987, Journal of cell science.

[42]  H. Broxmeyer,et al.  Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. , 1980, Blood.

[43]  M. Jäger,et al.  Bone marrow concentrate: a novel strategy for bone defect treatment. , 2009, Current stem cell research & therapy.

[44]  P. Janmey,et al.  Bone marrow-derived human mesenchymal stem cells become quiescent on soft substrates but remain responsive to chemical or mechanical stimuli. , 2009, Tissue engineering. Part A.

[45]  J. Fischer.  Mesenchymal Progenitor Cells , 2009 .

[46]  C. Heeschen,et al.  Concentration of bone marrow total nucleated cells by a point-of-care device provides a high yield and preserves their functional activity. , 2008, Cell transplantation.

[47]  D. Prockop,et al.  Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. , 2006, Cytotherapy.

[48]  A. Poignard,et al.  Percutaneous Autologous Bone-Marrow Grafting for Nonunions , 2005 .

[49]  W. Bonfield,et al.  Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes. , 2004, Journal of biomedical materials research. Part A.

[50]  Kevin McIntosh,et al.  Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. , 2002, Experimental hematology.

[51]  T. Orr,et al.  Compressive properties of cancellous bone defects in a rabbit model treated with particles of natural bone mineral and synthetic hydroxyapatite. , 2001, Biomaterials.