间充质细胞浓缩和骨修复：潜在的误区

dr.qinan

Mesenchymal Stem Cell Concentration and Bone Repair: Potential Pitfalls from Bench to Bedside

Anna V. Cuomo, MD1, Mandeep Virk, MBBS2, Frank Petrigliano, MD1, Elise F. Morgan, PhD3 and Jay R. Lieberman, MD2
1 David Geffen School of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, 16-155 CHS, Los Angeles, CA 90095
2 New England Musculoskeletal Institute, Department of Orthopaedic Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030. E-mail address for J.R. Lieberman: JLieberman@uchc.edu
3 Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston, MA 02215

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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 0.005) and significantly lower than those for Groups V and VI (p 0.001). The bone volume and mineral density did not differ among Groups III, IV, and V (p = 0.53). The percent total bone volume and percent normal bone volume in Group VI were significantly higher than those values in Groups I, III, and IV (p < 0.0001) and those in Group II (p = 0.048). In Groups II through V, the cortical bone was more dense than the lace-like bone in Group VI.

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.