Craniofacial repair with fetal bone grafts engineered from amniotic mesenchymal stem cells.
BACKGROUND
Ethically acceptable applications of fetal tissue engineering as a perinatal therapy can be expanded beyond life-threatening anomalies by amniotic fluid cell-based methods, in which cell procurement poses no additional risk to the mother. We sought to start to determine whether osseous grafts engineered from amniotic mesenchymal stem cells (aMSCs) could be an adjunct to craniofacial repair.


METHODS
New Zealand rabbits (n = 12) underwent creation of a full-thickness diploic nasal bone defect. We then equally divided animals into two groups based on how the defect was repaired: namely, size-matched implants of electrospun biodegradable nanofibers with or without nuclear labeled, allogeneic aMSCs maintained in osteogenic medium. We killed animals 8 wk post-implantation for multiple analyses. Statistical analysis included analysis of variance, post-hoc Bonferroni adjusted comparisons, and Levene's F-test, as appropriate (P < 0.05), with significance set at P < 0.05.


RESULTS
Micro-computed tomography scanning (two- and three-dimensional) showed no significant differences in defect radiodensity between groups. However, extracellular calcium levels were significantly higher in engineered grafts than in acellular implants (P = 0.003). There was significantly greater variability in mineralization in acellular implants than in engineered grafts by both direct calcium (P = 0.008) and micro-computed tomography measurements (P = 0.032). There were no significant differences in alkaline phosphatase activity or variance between groups. We documented labeled cells in the engineered grafts.


CONCLUSIONS
Craniofacial repair with osseous grafts engineered from aMSCs lead to enhanced and more consistent mineralization compared with an equivalent acellular prosthetic repair. Amniotic fluid-derived engineered bone may become a practical adjunct to perinatal craniofacial reconstruction.
Department of Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
Christopher G
CG
Turner
Justin D
JD
Klein
Fabienne L
FL
Gray
Azra
A
Ahmed
David
D
Zurakowski
Dario O
DO
Fauza
D000469:Alkaline Phosphatase / Q000378:metabolism; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D016025:Bone Transplantation; D019465:Craniofacial Abnormalities / Q000601:surgery; D005147:Facial Bones / Q000601:surgery*; D016332:Fetal Tissue Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011817:Rabbits; D012886:Skull / Q000601:surgery*; D023822:Tissue Engineering / Q000379:methods*; D014057:Tomography, X-Ray Computed
D000469:Alkaline Phosphatase