Systematically transplanted human gingiva-derived mesenchymal stem cells regulate lipid metabolism and inflammation in hyperlipidemic mice with periodontitis

Xiaoxuan Liu; Zhiguo Wang; Wenbin Song; Wendong Sun; Rundan Hong; Anita Pothukuchi; Quanchen Xu

doi:10.3892/etm.2019.8256

Systematically transplanted human gingiva-derived mesenchymal stem cells regulate lipid metabolism and inflammation in hyperlipidemic mice with periodontitis

Exp Ther Med. 2020 Jan;19(1):672-682. doi: 10.3892/etm.2019.8256. Epub 2019 Nov 29.

Authors

Xiaoxuan Liu^{1

2}, Zhiguo Wang³, Wenbin Song¹, Wendong Sun¹, Rundan Hong¹, Anita Pothukuchi⁴, Quanchen Xu¹

Affiliations

¹ Department of Stomatology, Dental Digital Medicine and 3D Printing Engineering Laboratory of Qingdao University, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
² Department of Stomatology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.
³ Department of Burn and Plastic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
⁴ Department of Physical and Biological Sciences, University of California, Santa Cruz, CA 95064, USA.

Abstract

Gingiva-derived mesenchymal stem cells (GMSCs) have been the focus of extensive research due to their numerous distinct properties, including their homing to injury sites and their contribution to tissue regeneration. However, the role of transplanted GMSCs in the regulation of lipid metabolism and inflammation in hyperlipidemic mice with periodontitis has not been demonstrated. In the present study, apolipoprotein E-deficient (ApoE^-/-) mice were used to establish a hyperlipidemia model with periodontitis and divided into two groups: Group B and Group C (n=20 per group), and wild-type C57BL/6J mice without any treatment were assigned to Group A (n=20). Animals in Group C were then injected with human GMSCs through the tail vein and animals in Group B were injected with α-MEM as control. Animals were sacrificed at indicated time points. Serum was collected to determine the lipids and inflammatory cytokines. Liver samples were collected to estimate lipid-associated gene expression. Morphometric and histological analyses were performed to maxillaries. The results demonstrated that the delivery of GMSCs led to a significant decrease in triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL), interleukin (IL)-6, tumor necrosis factor (TNF)-α, alveolar bone loss (ABL), and sterol regulatory element binding protein-1c (SREBP-1c) mRNA, and a significant increase in high density lipoprotein cholesterol (HDL), IL-10 and peroxisome proliferator-activated receptor α (PPARα) mRNA in Group C compared to Group B. Histological examination showed increased formation of new bone and higher alveolar bone height in Group C. Systematically transplanted GFP-positive cells were detected through both fluorescence microscope observation and immunohistochemical staining in the periodontal tissues. Overall, systematically transplanted GMSCs attenuated the hyperlipidemia and inflammatory responses in hyperlipidemic mice with periodontitis, and improved periodontal tissue regeneration.

Keywords: gingiva; hyperlipidemia; mesenchymal stem cells; periodontitis; systematical transplantation.