Quan-Chen Xu1, Peng-Jie Hao2, Xin-Bo Yu3, Shu-Lan Chen4, Mei-Jiao Yu5, Jin Zhang5, Pi-Shan Yang6. 1. 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. 2. Yantai Stomatological Hospital Yantai, China. 3. The Affiliated Hospital of Qingdao University Medical College Qingdao, China. 4. Qingdao Municipal Hospital Qingdao, China. 5. Shandong Provincial Key Laboratory of Oral Biomedicine, Shandong University Jinan, China ; Department of Endodontics, School of Dentistry, Shandong University Jinan, China. 6. Department of Periodontology, School of Dentistry, Shandong University Jinan, China ; Shandong Provincial Key Laboratory of Oral Biomedicine, Shandong University Jinan, China.
Abstract
PURPOSE: 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.
PURPOSE: 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.
Entities:
Keywords:
Hyperlipidemia; bone regeneration; homing efficiency; mesenchymal stem cells; mice
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