title: Mesenchymal stem cells attenuated PLGA-induced inflammatory responses by inhibiting host DC maturation and function.
abstract: The poly lactic-co-glycolic acid (PLGA) bio-scaffold is a biodegradable scaffold commonly used for tissue repair. However, implanted PLGA scaffolds usually cause serious inflammatory responses around grafts. To improve PLGA scaffold-based tissue repair, it is important to control the PLGA-mediated inflammatory responses. Recent evidence indicated that PLGA induce dendritic cell (DC) maturation in vitro, which may initiate host immune responses. In the present study, we explored the modulatory effects of mesenchymal stem cells (MSC) on PLGA-induced DCs (PLGA-DC). We found that mouse MSCs inhibited PLGA-DC dendrite formation, as well as co-stimulatory molecule and pro-inflammatory factor expression. Functionally, MSC-educated PLGA-DCs promoted Th2 and regulatory T cell differentiation but suppressed Th1 and Th17 cell differentiation. Mechanistically, we determined that PLGA elicited DC maturation via inducing phosphorylation of p38/MAPK and ERK/MAPK pathway proteins in DCs. Moreover, MSCs suppressed PLGA-DCs by partially inactivating those pathways. Most importantly, we found that the MSCs were capable of suppressing DC maturation and immune function in vivo. Also, the proportion of mature DCs in the mice that received MSC-PLGA constructs greatly decreased compared with that of their PLGA-film implantation counterparts. Additionally, MSCs co-delivery increased regulatory T and Th2 cells but decreased the Th1 and Th17 cell numbers in the host spleens. Histological analysis showed that MSCs alleviated the inflammatory responses around the grafted PLGA scaffolds. In summary, our findings reveal a novel function for MSCs in suppressing PLGA-induced host inflammatory response and suggest that DCs are a new cellular target in improving PLGA scaffold-based tissue repair.
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China. Electronic address: zhudingdingabc@163.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: BNLMS, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun No. 1 Street, Haidian District, Beijing 100190, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.
authors.forename: Xi-Mei
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Chu
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.
authors.forename: Yuan-Lin
authors.initials: YL
authors.lastname: Liu
authors.affiliation: BNLMS, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun No. 1 Street, Haidian District, Beijing 100190, PR China.
authors.forename: Shen-Guo
authors.initials: SG
authors.lastname: Wang
authors.affiliation: BNLMS, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun No. 1 Street, Haidian District, Beijing 100190, PR China. Electronic address: dcwu@iccas.ac.cn.
authors.forename: De-Cheng
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China. Electronic address: zhang_yi612@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology / Q000276:immunology; D016130:Immunophenotyping; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D019344:Lactic Acid / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Dendritic cells; Host inflammatory responses; Mesenchymal stem cells; Poly (lactide-co-glycolide)