Xu Quan-Chen, Hao Peng-Jie, Yu Xin-Bo, Chen Shu-Lan, Yu Mei-Jiao, Zhang Jin, Yang Pi-Shan
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.
Yantai Stomatological Hospital Yantai, China.
Int J Clin Exp Pathol. 2014 Mar 15;7(4):1580-7. eCollection 2014.
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.
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.
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.
Hyperlipidemia compromises homing efficiency of systemically transplanted BMSCs and inhibits bone regeneration.
间充质干细胞（MSCs）可选择性归巢至骨缺损部位，并在促进骨再生中发挥重要作用。高脂血症作为骨代谢的不良影响因素，会显著损害骨再生。在本研究中，将骨髓基质细胞（BMSCs）全身移植到高脂血症小鼠模型中，以探讨高脂血症对干细胞募集和骨再生的影响。
通过给C57BL/6J背景的ApoE-/-小鼠喂食高脂饮食（HFD）5周来建立高脂血症模型。以相同饮食喂养的C57BL/6小鼠作为对照。然后经尾静脉注射绿色荧光蛋白（GFP）标记的BMSCs，并在下颌骨制造骨缺损。在术后第1、2和4周处死动物，通过荧光显微镜和免疫组织化学分析监测移植的BMSCs的命运。经过苏木精-伊红（HE）染色和Masson三色（MT）染色后，进行组织形态计量分析以评估骨再生情况。
在两组移植BMSCs的小鼠中，骨缺损处检测到的GFP阳性BMSCs数量在术后1周达到峰值，此后减少。然而，在所有时间点，ApoE-/-小鼠中检测到的GFP+细胞均少于相应的对照小鼠。BMSCs移植显著促进了新骨形成，但与对照小鼠相比，ApoE-/-小鼠中的促进程度较小。
高脂血症会损害全身移植的BMSCs的归巢效率并抑制骨再生。
