Culture-Expanded, Bone Marrow-Derived Mesenchymal Stem Cells Can Regenerate a Critical-Sized Segmental Bone Defect

Abstract

Bone marrow has been shown to contain a population of rare cells capable of differentiating into the cells that form bone, cartilage, and other connective tissues. These cells, referred to as mesenchymal stem cells (MSCs), can be purified and culture-expanded from bone marrow, and are capable of forming bone when implanted ectopically in an appropriate carrier. To test the ability of MSCs to heal a critical-sized segmental defect, syngeneic culture-expanded MSCs were loaded onto a porous cylinder of hydroxyapatite/tricalcium phosphate (HA/TCP) and implanted in an 8-mm segmental defect in the femora of adult rats. For comparison, other defects received either marrow-loaded or cell-free HA/TCP cylinders, or no implant. The healing response was evaluated at 4 and 8 weeks by radiography, histology, and quantitative histomorphometry. Defects that received no implant, cell-free HA/TCP cylinders, or cylinders loaded with fresh marrow failed to heal by 8 weeks. In contrast, defects that received MSC-loaded cylinders showed significantly more bone formation at 4 weeks, and were completely healed by 8 weeks with excellent union of the host-implant interfaces. Histomorphometry demonstrates that bone fill in MSC-loaded implants (43%) is greater (p < 0.05) than that obtained with marrow-loaded (19%) or cell-free implants (10%).