BONE REGENERATION BY IMPLANTATION OF PURIFIED, CULTURE-EXPANDED HUMANMESENCHYMAL STEM-CELLS

Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage, tendon, and other connective tis sues. These cells, referred to as mesenchymal stem cells, can be purif ied and culture-expanded from animals and humans and have been shown t o regenerate functional tissue when delivered to the site of musculosk eletal defects in experimental animals. To test the ability of purifie d human mesenchymal stem cells to heal a clinically significant bone d efect, mesenchymal stem cells isolated from normal human bone marrow w ere culture-expanded, loaded onto a ceramic carrier, and implanted int o critical-sized segmental defects in the femurs of adult athymic rats . For comparison, cell-free ceramics were implanted in the contralater al limb. The animals were euthanized at 4, 8, or 12 weeks, and healing bone defects were compared by high-resolution radiography, immunohist ochemistry, quantitative histomorphometry, and biomechanical testing. In mesenchymal stem cell-loaded samples, radiographic and histologic e vidence of new bone was apparent by 8 weeks and histomorphometry demon strated increasing bone formation through 12 weeks. Biomechanical eval uation confirmed that femurs implanted with mesenchymal stem cell-load ed ceramics were significantly stronger than those that received cell- free ceramics. These studies demonstrate that human mesenchymal stem c ells can regenerate bone in a clinically significant osseous defect an d may therefore provide an alternative to autogenous bone grafts.