Plastic Surgery Research Council
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STEM CELL THERAPY REMEDIATES MANDIBULAR VASCULOGENESIS FOLLOWING RADIATION AND DISTRACTION OSTEOGENESIS
Presenter: Sagar S Deshpande, BS
Co-Authors: Donneys A; Gallagher KK; Tchanque-Fossuo CN; Felice PA; Sun HL; Krebsbach PH; Buchman SR
University of Michigan Medical School

Purpose: Radiation therapy is known to be detrimental to bone and soft tissue repair, resulting in an unacceptably high incidence of devastating wound healing complications. This is effected through a mechanism of both direct cellular and vascular depletion. Bone marrow stromal cells (BMSCs) have previously been show to enhance the generation of new bone during distraction osteogenesis (DO) following radiation (XRT). We posit that transplanted BMSCs will be able to augment the mandibular vascularity devastated by XRT therapy.

Methods: 19 male Lewis rats were randomly split into three groups, DO (n=5), XRT/DO (n=7) and BMSC (n=7). XRT and DO underwent 5 day fractionated XRT of the left mandible at 7 Gy per day and were allowed to recover for two weeks. All groups underwent mandibular distractor placement. The BMSC group received a Surgifoam scaffold with 2 million BMSCs intra-operatively placed within the distraction gap. Groups were distracted at 0.3mm every 12 hrs to a 5.1mm (a critical-sized defect for an irradiated, distracted mandible), and sacrificed on post-operative day 40. An ANOVA with post-hoc Tukey or Games-Howell tests were utilized, depending on data homogeneity.

Results: Intraoperative transplantation of BMSCs significantly improves the vessel volume fraction (VVF, cc/cc), vessel number (VN, 1/mm), vessel separation (VS, mm), vessel thickness (VT, mm), and degree of anisotropy (DA, unitless) of vessels within the region of interest over XRT/DO specimens, with no difference between BMSC and DO.

Conclusion: The vascular environment of bone is essential for its capacity to heal. These results indicate that administration of BMSCs intra-operatively to an irradiated distraction gap produces regenerate with superior metrics of vascular quality and restoring it to near-DO levels. Most interestingly, radiation prevents the vascular anisotropy typically induced by DO. BMSC treatment reverses XRT-induced vascular isotropy and allows angiogenesis to respond to the mechanotransductive pathways induced by DO.


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