title: Therapeutic effect of TSG-6 engineered iPSC-derived MSCs on experimental periodontitis in rats: a pilot study.
abstract: 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-1β and TNF-α 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.
authors: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan, China.
authors: Heng
authors: H
authors: Yang
authors: Center for Dental Research, Loma Linda University School of Dentistry, Loma Linda, California, United States of America.
authors: Raydolfo M
authors: RM
authors: Aprecio
authors: Center for Dental Research, Loma Linda University School of Dentistry, Loma Linda, California, United States of America.
authors: Xiaodong
authors: X
authors: Zhou
authors: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan, China.
authors: Qi
authors: Q
authors: Wang
authors: Center for Dental Research, Loma Linda University School of Dentistry, Loma Linda, California, United States of America.
authors: Wu
authors: W
authors: Zhang
authors: Department of Periodontology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors: Yi
authors: Y
authors: Ding
authors: Center for Dental Research, Loma Linda University School of Dentistry, Loma Linda, California, United States of America.
authors: Yiming
authors: Y
authors: Li
mesh_terms: D000287:Administration, Topical; D016301:Alveolar Bone Loss / Q000235:genetics / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D016866:Bacteroidaceae Infections / Q000235:genetics / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D060846:Cell Engineering; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D007275:Injections, Intravenous; D053583:Interleukin-1beta / Q000097:blood; D008437:Maxilla / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008963:Molar / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D010010:Osteoclasts / Q000382:microbiology / Q000473:pathology; D010518:Periodontitis / Q000235:genetics / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D016966:Porphyromonas gingivalis / Q000472:pathogenicity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015815:Cell Adhesion Molecules; D053583:Interleukin-1beta; C513056:Tnfaip6 protein, rat; D014409:Tumor Necrosis Factor-alpha