Sagar S Deshpande1, Kathleen K Gallagher, Alexis Donneys, Noah S Nelson, Nicholas P Guys, Peter A Felice, Erin E Page, Hongli Sun, Paul H Krebsbach, Steven R Buchman. 1. 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.
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.
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: Kevin M Urlaub; Russell E Ettinger; Noah S Nelson; Jessie M Hoxie; Alicia E Snider; Joseph E Perosky; Yekaterina Polyatskaya; Alexis Donneys; Steven R Buchman Journal: J Craniofac Surg Date: 2019 Mar/Apr Impact factor: 1.046
Authors: Edward G Carey; Sagar S Deshpande; Kevin M Urlaub; Alexander R Zheutlin; Noah S Nelson; Alexis Donneys; Stephen Y Kang; Kathleen K Gallagher; Peter A Felice; Catherine N Tchanque-Fossuo; Steven R Buchman Journal: J Craniofac Surg Date: 2017-06 Impact factor: 1.046
Authors: Alexander R Zheutlin; Sagar S Deshpande; Noah S Nelson; Yekaterina Polyatskaya; Jose J Rodriguez; Alexis Donneys; Steven R Buchman Journal: J Oral Maxillofac Surg Date: 2015-08-07 Impact factor: 1.895
Authors: Jeremy V Lynn; Kavitha Ranganathan; Kevin M Urlaub; Alexandra O Luby; Chris J Stephan; Alexis Donneys; Noah S Nelson; Steven R Buchman Journal: Ann Plast Surg Date: 2020-07 Impact factor: 1.763