title: Stem cells rejuvenate radiation-impaired vasculogenesis in murine distraction osteogenesis.
abstract: BACKGROUND
  Radiotherapy is known to be detrimental to bone and soft-tissue repair. Bone marrow stromal cells have been shown to enhance bone regeneration during distraction osteogenesis following radiation therapy. The authors posit that transplanted bone marrow stromal cells will significantly augment the mandibular vascularity devastated by radiation therapy.
  
  
  METHODS
  Nineteen male Lewis rats were split randomly into three groups: distraction osteogenesis only (n = 5), radiation therapy plus distraction osteogenesis (n = 7), and radiation therapy plus distraction osteogenesis with intraoperative placement of 2 million bone marrow stromal cells (n = 7). A mandibular osteotomy was performed, and an external fixator device was installed. From postoperative days 4 through 12, rats underwent a gradual 5.1-mm distraction followed by a 28-day consolidation period. On postoperative day 40, Microfil was perfused into the vasculature and imaging commenced. Vascular radiomorphometric values were calculated for regions of interest. An analysis of variance with post hoc Tukey or Games-Howell tests was used, dependent on data homogeneity.
  
  
  RESULTS
  Stereologic analysis indicated significant remediation in vasculature in the bone marrow stromal cell group compared with the radiation therapy/distraction osteogenesis group. Each of five metrics idicated significant improvements from radiation therapy/distraction osteogenesis to the bone marrow stromal cell group, with no difference between the bone marrow stromal cell group and the distraction osteogenesis group.
  
  
  CONCLUSIONS
  Bone marrow stromal cells used together with distraction osteogenesis can rejuvenate radiation-impaired vasculogenesis in the mandible, reversing radiation therapy-induced isotropy and creating a robust vascular network. Bone marrow stromal cells may offer clinicians an alternative reconstructive modality that could improve the lifestyle of patients with hypovascular bone.
authors.affiliation: Ann Arbor, Mich.; and Charleston, S.C. From the Craniofacial Research Laboratory, the Department of Otolaryngology, and the Section of Plastic Surgery, Department of Surgery, University of Michigan Health System; the University of Michigan Medical School; the College of Literature, Sciences, and the Arts, University of Michigan; the Division of General Surgery, Department of Surgery, Medical University of South Carolina; and the Department of Biologic and Materials Sciences, University of Michigan Dental School.
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: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Guys
authors.forename: Peter A
authors.initials: PA
authors.lastname: Felice
authors.forename: Erin E
authors.initials: EE
authors.lastname: Page
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; D001854:Bone Marrow Cells / Q000166:cytology; D001861:Bone Regeneration; D008297:Male; D008334:Mandible / Q000528:radiation effects / Q000601:surgery*; D018919:Neovascularization, Physiologic / Q000528:radiation effects*; D019857:Osteogenesis, Distraction / Q000379:methods*; D010025:Osteoradionecrosis / Q000473:pathology / Q000601:surgery*; D011833:Radiation Injuries, Experimental; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation / Q000379:methods*