Evaluation of mesenchymal stem cells following implantation in alveolar sockets: a canine safety study.
OBJECTIVE
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.


METHODS
MSCs isolated from bone marrow aspirations were culture-expanded and cryopreserved. Thawed cells were incubated with 3.2 x 5-mm hydroxyapatite/tricalcium phosphate (HA/TCP) cylinders in a closed system containing 5 x 10(7) 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.


CONCLUSIONS
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.
De Kok
Ingeborg J
IJ
Department of Prosthodontics, University of North Carolina, Chapel Hill, North Carolina, USA.
Drapeau
Susan J
SJ
Young
Randell
R
Cooper
Lyndon F
LF
D000818:Animals; D001861:Bone Regeneration; D002130:Calcium Phosphates; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D004285:Dogs; D017886:Durapatite; D045164:Mesenchymal Stem Cell Transplantation; D023421:Models, Animal; D012449:Safety; D023822:Tissue Engineering; D020390:Tooth Socket
D002130:Calcium Phosphates; D017886:Durapatite; C018392:tricalcium phosphate