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Summary:Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage. tendon, and other connective tissues. These cells. referred to as mesenchymal stem cells, can be purified and culture-expanded from animals and humans and have been shown to regencrate functional tissue when delivered to the site of musculoskeletal defects in experimental animal$. To test the ability of purified human mesenchymal stem cells to heal a clinically significant bone defect, mesenchymal stem cells isolated from normal human bone marrow were culture-expanded, loaded onto a ceramic carrier, and implanted into critical-sized segmental defects in the femurs of adult athymic rats. For comparison, cell-free ceramics were implanted in the contralateral limb. The animals were euthanized at 4,8, or 12 weeks, and healing bone defects were compared by high-resolution radiography, immunoliistochemistry. quantitative histomorphometry. and biomechanical testing. In mesenchymal stem cell-loaded samples, radiographic and histologic evidence of new bone was apparent by 8 weeks and histoniorphometry demonstrated increasing bone formation through 12 weeks. Biomechanical evaluation confirmed that femurs implanted with mesenchymal stem cell-loaded ceramics were significantly stronger than those that received cell-lree ceramics. These studies demonstrate that human mesenchymal stern cells can regenerate bone in a clinically significant osscous defect and may therefore provide an alternative to autogcnous bone grafts.

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