title: Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis: A histomorphometric evaluation.
abstract: The purpose of this study is to determine if intraoperatively placed bone marrow stem cells (BMSCs) will permit successful osteocyte and mature bone regeneration in an isogenic murine model of distraction osteogenesis (DO) following radiation therapy (XRT). Lewis rats were split into three groups, DO only (Control), XRT followed by DO (xDO) and XRT followed by DO with intraoperatively placed BMSCs (xDO-BMSC). Coronal sections from the distraction site were obtained, stained and analyzed via statistical analysis with analysis of variance (ANOVA) and subsequent Tukey or Games-Howell post-hoc tests. Comparison of the xDO-BMSC and xDO groups demonstrated significantly improved osteocyte count (87.15 ± 10.19 vs. 67.88 ± 15.38, P = 0.00), and empty lacunae number (2.18 ± 0.79 vs 12.34 ± 6.61, P = 0.00). Quantitative analysis revealed a significant decrease in immature osteoid volume relative to total volume (P = 0.00) and improved the ratio of mature woven bone to immature osteoid (P = 0.02) in the xDO-BMSC compared with the xDO group. No significant differences were found between the Control and xDO-BMSC groups. In an isogenic murine model of DO, BMSC therapy assuaged XRT-induced cellular depletion, resulting in a significant improvement in histological and histomorphometric outcomes.
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Zheutlin
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA; Department of Otolaryngology, Ohio State University, Columbus, OH, USA.
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA; Department of Otolaryngology, Baylor University, Houston, TX, USA.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Gallagher
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Yekaterina
authors.initials: Y
authors.lastname: Polyatskaya
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Rodriguez
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Ranganathan
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA. Electronic address: sbuchman@med.umich.edu.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001861:Bone Regeneration / Q000502:physiology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008334:Mandible / Q000254:growth & development* / Q000528:radiation effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D010011:Osteocytes / Q000166:cytology*; D019857:Osteogenesis, Distraction / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew
keywords: histology; mandible; osteocyte; radiotherapy