TY - JOUR
T1 - Therapeutic effect of TSG-6 engineered iPSC-derived MSCs on experimental periodontitis in rats
T2 - A pilot study
AU - Yang, Heng
AU - Aprecio, Raydolfo M.
AU - Zhou, Xiaodong
AU - Wang, Qi
AU - Zhang, Wu
AU - Ding, Yi
AU - Li, Yiming
N1 - 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.
PY - 2014/6/30
Y1 - 2014/6/30
N2 - 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 iPSCMSC/ 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.
AB - 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 iPSCMSC/ 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.
KW - Gene Expression
KW - Injections, Intravenous
KW - Transduction, Genetic
KW - Maxilla/metabolism
KW - Rats
KW - Interleukin-1beta/blood
KW - Rats, Sprague-Dawley
KW - Mesenchymal Stem Cells/cytology
KW - Induced Pluripotent Stem Cells/cytology
KW - Porphyromonas gingivalis/pathogenicity
KW - Animals
KW - Osteoclasts/microbiology
KW - Tumor Necrosis Factor-alpha/blood
KW - Molar/metabolism
KW - Cell Engineering
KW - Female
KW - Periodontitis/genetics
KW - Cell Adhesion Molecules/genetics
KW - Cell Differentiation
KW - Administration, Topical
KW - Alveolar Bone Loss/genetics
KW - Bacteroidaceae Infections/genetics
KW - Mesenchymal Stem Cell Transplantation
KW - Disease Models, Animal
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UR - https://www.mendeley.com/catalogue/ff7fe569-e7eb-34de-8e98-3edbcbc1301d/
U2 - 10.1371/journal.pone.0100285
DO - 10.1371/journal.pone.0100285
M3 - Article
C2 - 24979372
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e100285
ER -