title: Mesenchymal stem cells and endothelial progenitor cells stimulate bone regeneration and mineral density.
abstract: BACKGROUND
  Alveolar bone deficiency is a major clinical problem in maxillofacial reconstructive surgery. The available surgical techniques to enhance extracortical bone augmentation are generally unpredictable and not satisfying. The aim of the present study is to quantify extracortical bone augmentation and tissue mineral density (TMD) after cotransplantation of peripheral blood-derived endothelial progenitor cells (EPCs) and bone marrow-derived mesenchymal stem cells (MSCs) by microcomputed tomography (micro-CT).
  
  
  METHODS
  Bone regeneration was tested in the guided bone regeneration rat calvaria model. Gold domes filled with beta tricalcium phosphate (β-TCP; control [CNT]) or β-TCP mixed with 5 × 10(5) rat EPCs and 5 × 10(5) rat osteogenic transformed MSCs (EPC/otMSCs) were fixed to the exposed calvaria. Rats were sacrificed after 3 months. Bone volume fraction (BV/TV) and TMD were analyzed using micro-CT. In the middle of the dome, a cylindrical region of interest was defined (it represents the area in which implants are placed) and subdivided into bottom, middle, and top to analyze the effect of the distance from the calvaria on bone formation.
  
  
  RESULTS
  In the whole cylinder, BV/TV and TMD were higher in the EPC/otMSC group compared with CNT (BV/TV: 22.9% ± 4.4% versus 29.1 ± 2.2%, P = 0.02; TMD: 937.79 ± 18.68 versus 960.78 ± 5.8 mgHA/ccm, P = 0.03; CNT versus EPC/otMSC, respectively). In each of the three subregions, BV/TV was higher in the EPC/otMSC group compared with CNT (top: 20.25% ± 2.4% versus 23.74% ± 1.5%, P = 0.007; middle: 23.2% ± 4.8% versus 28% ± 2.2%, P = 0.05; bottom: 25.3% ± 7.6% versus 35.7% ± 4.9%, P = 0.02; CNT versus EPC/otMSC, respectively).
  
  
  CONCLUSIONS
  Three-dimensional quantification by micro-CT demonstrated that cotransplantation of EPC/otMSCs significantly improved bone formation and mineral density.
authors.affiliation: Department of Periodontology, School of Graduate Dentistry, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Zigdon-Giladi
authors.forename: Tova
authors.initials: T
authors.lastname: Bick
authors.forename: Dina
authors.initials: D
authors.lastname: Lewinson
authors.forename: Eli E
authors.initials: EE
authors.lastname: Machtei
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D015519:Bone Density / Q000502:physiology*; D001861:Bone Regeneration / Q000502:physiology*; D002130:Calcium Phosphates / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology*; D005353:Fibronectins / Q000737:chemistry; D048091:Guided Tissue Regeneration / Q000295:instrumentation / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D010294:Parietal Bone / Q000601:surgery; D051381:Rats; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D005353:Fibronectins; C485817:beta-tricalcium phosphate
keywords: Adult stem cells; bone regeneration; endothelial cells; mesenchymal stromal cells; tissue engineering; x-ray microtomography