Tooth Socket Model for Mesenchymal Stem Cell Bone Regeneration

Tooth Socket Model for Mesenchymal Stem Cell Bone Regeneration
I.J. DE KOK, University of North Carolina, Chapel Hill, USA, and L.F. COOPER, University of North Carolina School of Dentistry, Chapel Hill, USA
2003
IADR
The use of bone marrow stromal derived mesenchymal stem cells (MSC) for alveolar or craniofacial repair is a proximal goal of tissue engineers. Based on an ectopic model in immunocompromised mice, a construct including culture-expanded, cryopreserved MSCs adherent to a porous HA/TCP scaffold was developed. Objective: to develop a clinical model of bone regeneration to evaluate the safety and estimate the efficacy of an MSC-based bone tissue engineering construct. Methods: MSCs isolated from bone marrow aspirations were culture expanded and cryopreserved. Thawed cells were incubated with 3.2 x 5mm HA/TCP cylinders in a closed system containing 5 x 107 cells/ml. Cells alone, or cell-free and cell loaded constructs were rinsed in saline and implanted in extraction sockets of 14 beagle dogs. Acute reactions were evaluated histologically after 7 or 21 days and bone formation was examined after 49 days. Bone formation was measured using Histomophometry (Bioquant). In a subsequent, IRB approved human clinical trial, four patients received autogenous cell-loaded constructs that were explanted 12 weeks following tooth extraction. Results: In the canine model, MSC-related inflammation, MSC-migration and ectopic osteogenesis were not observed. Wound dehiscence was a complication associated with cell exclusionary membranes and resulted in local inflammation. Measured bone formation was 34%, 25%, and 35% for cell-loaded, cell-free and untreated sockets, respectively (p<0.05). Early clinical data indicate the absence of inflammation or adverse events, alveolar preservation, and osteogenesis in cell-loaded constructs at the 12 week period. Conclusion: The tooth socket model offers select advantages for early clinical evaluation of the safety and efficacy of MSC-based tissue engineering of bone. Supported by Osiris Therapeutics, Inc. Baltimore MD.