J Bone Joint Surg Am 2009 May;91(5):1073-83
David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Background: Mesenchymal stem cells are multipotent and have the ability to differentiate into bone. We conducted a preclinical trial comparing the osteogenic potential of human bone marrow aspirate with that of mesenchymal stem cell-enriched bone marrow aspirate (both mixed with demineralized bone matrix) in a critical-sized rat femoral defect model.
Methods: The buffy coat was extracted from human bone marrow aspirate to obtain mesenchymal stem cell-enriched bone marrow aspirate. Fifty-nine athymic rats, each with a 6-mm femoral defect, were divided into six treatment groups: defect only (Group I), demineralized bone matrix and saline solution (Group II), demineralized bone matrix and bone marrow aspirate (Group III), demineralized bone matrix and mesenchymal stem cell-enriched bone marrow aspirate (Group IV), demineralized bone matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2) (Group V [positive control]), and absorbable collagen sponge and rhBMP-2 (Group VI [positive control]). All animals were killed at twelve weeks for radiographic, micro-computed tomography, histomorphometric, and histologic analysis.
Results: There was wide variability in the mesenchymal stem cell concentrations obtained from the human donors. All ten defects healed in the positive control groups (Groups V and VI). Only one defect healed in each experimental group (Groups II, III, and IV) (i.e., three of forty-four defects healed). There was no significant difference among the radiographic scores of Groups II, III, and IV (p = 0.59), and the score for each of those groups was significantly higher than that for Group I (p
Conclusions: Neither bone marrow aspirate nor mesenchymal stem cell-enriched bone marrow aspirate mixed with demineralized bone matrix resulted in reliable healing of critical-sized bone defects. It is possible that a greater number of mesenchymal stem cells or an enhanced osteoinductive signal is required for adequate bone-healing. Mesenchymal stem cell and/or carrier variability may also contribute to differences in bone formation.