Therapeutic Effect of TSG-6 Engineered iPSC-Derived MSCs on Experimental Periodontitis in Rats: A Pilot Study

被引：59

作者：

Yang, Heng ^{[1
]}

Aprecio, Raydolfo M. ^{[2
]}

Zhou, Xiaodong ^{[2
]}

Wang, Qi ^{[1
]}

Zhang, Wu ^{[2
]}

Ding, Yi ^{[3
]}

Li, Yiming ^{[2
]}

机构：

[1] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610064, Sichuan, Peoples R China

[2] Loma Linda Univ, Sch Dent, Dent Res Ctr, Loma Linda, CA 92350 USA

[3] Sichuan Univ, Dept Periodontol, West China Hosp Stomatol, Chengdu 610064, Sichuan, Peoples R China

来源：

PLOS ONE | 2014年 / 9卷 / 06期

关键词：

PLURIPOTENT STEM-CELLS; ANTIINFLAMMATORY PROTEIN TSG-6; INTER-ALPHA-INHIBITOR; MARROW STROMAL CELLS; LINK MODULE; IN-VIVO; BONE; REGENERATION; INFLAMMATION; GENERATION;

D O I：

10.1371/journal.pone.0100285

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background: We derived mesenchymal stem cells (MSCs) from rat induced pluripotent stem cells (iPSCs) and transduced them with tumor necrosis factor alpha-stimulated gene-6 (TSG-6), to test whether TSG-6 overexpression would boost the therapeutic effects of iPSC-derived MSCs in experimental periodontitis. Methods: A total of 30 female Sprague-Dawley (SD) rats were randomly divided into four groups: healthy control group (Group-N, n = 5), untreated periodontitis group (Group-P, n = 5), iPS-MSCs-treated and iPSC-MSCs/TSG-6-treated periodontitis groups (Group-P1 and P2, n = 10 per group). Experimental periodontitis was established by ligature and infection with Porphyromonas gingivalis around the maxillae first molar bilaterally. MSC-like cells were generated from rat iPSCs, and transducted with TSG-6. iPSC-MSCs or iPSC-MSCs/TSG-6 were administrated to rats in Group-P1 or P2 intravenously and topically, once a week for three weeks. Blood samples were obtained one week post-injection for the analysis of serum pro-inflammatory cytokines. All animals were killed 3 months post-treatment; maxillae were then dissected for histological analysis, tartrate-resistant acid phosphatase (TRAP) staining, and morphological analysis of alveolar bone loss. Results: Administration of iPSC-MSC/TSG-6 significantly decreased serum levels of IL-1 beta and TNF-alpha in the Group-P2 rats (65.78 pg/ml and 0.56 pg/ml) compared with those in Group-P (168.31 pg/ml and 1.15 pg/ml respectively) (p<0.05). Both alveolar bone loss and the number of TRAP-positive osteoclasts showed a significant decrease in rats that received iPSC-MSC/TSG-6 treatment compared to untreated rats in Group-P (p<0.05), Conclusions: We demonstrated that overexpression of TSG-6 in rat iPSC-derived MSCs were capable of decreasing inflammation in experimental periodontitis and inhibiting alveolar bone resorption. This may potentially serve as an alternative stem-cell-based approach in the treatment and regeneration of periodontal tissues.

引用

页数：7

共 37 条

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Periodontitis deteriorates metabolic control in type 2 diabetic Goto-Kakizaki rats [J].