Evaluation of Mesenchymal Stem Cells Following Implantation in Alveolar Sockets: A Canine Safety Study

Purpose: The overall goal of this project was to evaluate culture-expanded bone-marrow-derived mesenchymal stem cells (MSCs) for alveolar bone repair in terms of safety and potential efficacy. Materials and Methods: MSCs isolated from bone marrow aspirations were culture-expanded and cryopreserved. Thawed cells were incubated with 3.2 3 5-mm hydroxyapatite/tricalcium phosphate (HA/TCP) cylinders in a closed system containing 5 3 107 cells/mL. Cells alone, cell-free constructs, or cell-loaded constructs were rinsed in saline and implanted in extraction sockets in the mandibular second and fourth premolar sites of 14 beagle dogs. Acute reactions were evaluated histologically after 7 or 21 days, and bone formation was examined after 49 days. Results: Neither implanted MSC-related inflammation nor ectopic osteogenesis was observed. At 7 and 21 days, dil-labeled canine MSCs were found in more than 80% of the implant sites. Few canine MSCs were found in neighboring tissue. Mild inflammation present at 7 days diminished by 21 days. After 49 days, measured bone formation was 34%, 25%, and 35% for cell-loaded, cell-free, and untreated sockets, respectively (P .05). At 21 days, bone formation was evident in all sites. Wound dehiscence was a complication associated with cell exclusionary membranes and resulted in local inflammation. Discussion: The extraction model indicates the safety of MSCs implanted adherent to HA/TCP. Local bone repair occurred in the absence of nonspecific differentiation or migration with distant osteogenesis. Conclusions: An alveolar socket model may be an appropriate model for initial clinical investigation of MSC-mediated bone repair.