title: Stem cell therapy remediates reconstruction of the craniofacial skeleton after radiation therapy.
abstract: This study utilized transplanted bone marrow stromal cells (BMSCs) as a cellular replacement therapy to remedy radiation-induced injury and restore impaired new bone formation during distraction osteogenesis (DO). BMSC therapy brought about the successful generation of new bone and significantly improved both the rate and quality of a bony union of irradiated, distracted [X-ray radiation therapy (XRT)/DO] murine mandibles to the level of nonirradiated DO animals. The bone mineral density and bone volume fraction were also significantly improved by the BMSC replacement therapy showing no difference when compared to nonirradiated animals. Finally, a biomechanical analysis examining the yield, failure load, and ultimate load also demonstrated a significantly improved structural integrity in BMSC-treated XRT/DO mandibles over XRT/DO alone. These results indicate that administration of BMSCs intraoperatively to a radiated distraction gap can function as an adequate stimulant to rescue the ability for irradiated bone to undergo DO and produce a healed regenerate of a vastly superior quality and strength. We believe that the fundamental information on the optimization of bone regeneration in the irradiated mandible provided by this work has immense potential to be translated from the bench to the bedside to lead to improved therapeutic options for patients suffering from the disastrous sequelae of radiation therapy.
authors.affiliation: Craniofacial Research Laboratory, Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Gallagher
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Tchanque-Fossuo
authors.forename: Deniz
authors.initials: D
authors.lastname: Sarhaddi
authors.forename: Hongli
authors.initials: H
authors.lastname: Sun
authors.forename: Paul H
authors.initials: PH
authors.lastname: Krebsbach
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D000818:Animals; D015519:Bone Density / Q000528:radiation effects; D001861:Bone Regeneration; D005147:Facial Bones / Q000528:radiation effects / Q000601:surgery; D008297:Male; D008334:Mandible / Q000528:radiation effects* / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D019857:Osteogenesis, Distraction; D051381:Rats; D011917:Rats, Inbred Lew; D012886:Skull / Q000528:radiation effects / Q000601:surgery; D023822:Tissue Engineering; D054457:Tissue Scaffolds