title: Hyperlipidemia compromises homing efficiency of systemically transplanted BMSCs and inhibits bone regeneration.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) can selectively home to bone defects and play an essential role in promoting bone regeneration. As an adverse effect factor for bone metabolism, hyperlipidemia significantly impairs bone regeneration. In this study, bone marrow stromal cells (BMSCs) were systemically transplanted into a hyperlipidemic mouse model to explore the effect of hyperlipidemia on stem cell recruitment and bone regeneration.
  
  
  METHODS
  Hyperlipidemia was established in ApoE-/- mice (on C57BL/6J background) fed with a high fat diet (HFD) for five weeks. C57BL/6 mice fed with the same diet served as controls. BMSCs labeled with the green fluorescent protein (GFP) were then injected via the tail vein and bone defects were created in the mandibles. The animals were sacrificed at weeks 1, 2 and 4 after surgery, and the fate of the transplanted BMSCs was monitored with a fluorescence microscope and immunohistochemical analysis. After hematoxylin and eosin (HE) staining and Masson's Trichrome (MT) staining, histomorphometric analysis was performed to evaluate bone regeneration.
  
  
  RESULTS
  In both groups transplanted with BMSCs, the number of GFP-positive BMSCs detected in the bone defects reached its peak at 1 week after surgery and was decreased thereafter. However, at all time points, less GFP+ cells were detected in the ApoE-/- mice than in the corresponding control mice. BMSCs transplantation significantly enhanced new bone formation, but to a lesser degree in the ApoE-/- mice when compared with the control mice.
  
  
  CONCLUSIONS
  Hyperlipidemia compromises homing efficiency of systemically transplanted BMSCs and inhibits bone regeneration.
authors.affiliation: Department of Periodontology, School of Dentistry, Shandong University Jinan, China ; The Affiliated Hospital of Qingdao University Medical College Qingdao, China ; Shandong Provincial Key Laboratory of Oral Biomedicine, Shandong University Jinan, China.
authors.forename: Quan-Chen
authors.initials: QC
authors.lastname: Xu
authors.affiliation: Yantai Stomatological Hospital Yantai, China.
authors.forename: Peng-Jie
authors.initials: PJ
authors.lastname: Hao
authors.affiliation: The Affiliated Hospital of Qingdao University Medical College Qingdao, China.
authors.forename: Xin-Bo
authors.initials: XB
authors.lastname: Yu
authors.affiliation: Qingdao Municipal Hospital Qingdao, China.
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Chen
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, Shandong University Jinan, China ; Department of Endodontics, School of Dentistry, Shandong University Jinan, China.
authors.forename: Mei-Jiao
authors.initials: MJ
authors.lastname: Yu
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, Shandong University Jinan, China ; Department of Endodontics, School of Dentistry, Shandong University Jinan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Periodontology, School of Dentistry, Shandong University Jinan, China ; Shandong Provincial Key Laboratory of Oral Biomedicine, Shandong University Jinan, China.
authors.forename: Pi-Shan
authors.initials: PS
authors.lastname: Yang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016026:Bone Marrow Transplantation; D001861:Bone Regeneration / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D006949:Hyperlipidemias / Q000209:etiology / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D049452:Green Fluorescent Proteins
keywords: Hyperlipidemia; bone regeneration; homing efficiency; mesenchymal stem cells; mice