Translational treatment paradigm for managing non-unions secondary to radiation injury utilizing adipose derived stem cells and angiogenic therapy.
Bony non-unions arising in the aftermath of collateral radiation injury are commonly managed with vascularized free tissue transfers. Unfortunately, these procedures are invasive and fraught with attendant morbidities. This study investigated a novel, alternative treatment paradigm utilizing adipose-derived stem cells (ASCs) combined with angiogenic deferoxamine (DFO) in the rat mandible.



Rats were exposed to a bioequivalent dose of radiation and mandibular osteotomy. Those exhibiting non-unions were subsequently treated with surgical debridement alone or debridement plus combination therapy. Radiographic and biomechanical outcomes were assessed after healing.



Significant increases in biomechanical strength and radiographic metrics were observed in response to combination therapy (p < .05). Importantly, combined therapy enabled a 65% reduction in persisting non-unions when compared to debridement alone.



We support the continued investigation of this promising combination therapy in its potential translation for the management of radiation-induced bony pathology. © 2015 Wiley Periodicals, Inc. Head Neck 38: E837-E843, 2016.
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
Alexis
A
Donneys
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
Jordan T
JT
Blough
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
Noah S
NS
Nelson
Orthopedic Research Laboratories, Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan.
Joseph E
JE
Perosky
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
Sagar S
SS
Deshpande
Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Stephen Y
SY
Kang
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.|Department of General Surgery, University of South Carolina School of Medicine, Columbia, South Carolina.
Peter A
PA
Felice
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
Christian
C
Figueredo
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
Jonathan R
JR
Peterson
Orthopedic Research Laboratories, Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan.
Kenneth M
KM
Kozloff
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
Benjamin
B
Levi
Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Douglas B
DB
Chepeha
Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
Steven R
SR
Buchman
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D003646:Debridement; D003676:Deferoxamine / Q000494:pharmacology*; D005599:Fractures, Ununited; D008334:Mandible / Q000528:radiation effects / Q000601:surgery*; D011832:Radiation Injuries / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology
D003676:Deferoxamine
adipose-derived stromal cell; deferoxamine; osteoradionecrosis; pathologic fracture; radiotherapy