title: Mesenchymal Stem Cell-Educated Macrophages Ameliorate LPS-Induced Systemic Response.
abstract: Both bone marrow and adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory effects. The goal of this study was to determine whether ASCs-educated macrophages could directly ameliorate LPS-induced systemic response in a mouse model. Mouse peritoneal macrophages were cocultured with ASCs in a Transwell system for 2 days to educate macrophages. Mice were divided into 5 groups: control, LPS, LPS + ASCs, LPS + untreated macrophages, and LPS + educated macrophages. Educated macrophages decreased lung inflammation, weight loss, pulmonary edema, and inflammatory cytokine response. In vitro, ASCs increased expression of M2 macrophages independent of direct cell-to-cell contact when macrophages were treated with LPS or serum from patients with acute respiratory distress syndrome (ARDS). When macrophages were cultured with serum from ARDS patients who were treated with ASCs or placebo in our previous clinical trial, there was no difference in M2 macrophage levels before and after ASCs treatment indicating a suboptimal response to the treatment protocol. ASCs also reduced the levels of LPS-induced proinflammatory cytokines in vitro which were mimicked by IL-10 and blocked by antibodies for IL-10 and IL-10 receptor supporting the notion that educated macrophages exert their anti-inflammatory effects via IL-10-dependent mechanisms.
authors.affiliation: The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China.
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China.
authors.forename: Chaojin
authors.initials: C
authors.lastname: Qin
authors.affiliation: Shaoxing Second Hospital, Shaoxing, Zhejiang 312000, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zheng
authors.affiliation: The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China.
authors.forename: Dengming
authors.identifier: 0000-0001-5470-9638
authors.initials: D
authors.lastname: Lai
authors.affiliation: The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China.
authors.forename: Huikang
authors.initials: H
authors.lastname: Tao
authors.affiliation: The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shaoxing Second Hospital, Shaoxing, Zhejiang 312000, China.
authors.forename: Guanguan
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Shaoxing Second Hospital, Shaoxing, Zhejiang 312000, China.
authors.forename: Menghua
authors.initials: M
authors.lastname: Ge
authors.affiliation: Shaoxing Second Hospital, Shaoxing, Zhejiang 312000, China.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Shaoxing Second Hospital, Shaoxing, Zhejiang 312000, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Cheng
authors.affiliation: The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China.
authors.forename: Qiang
authors.identifier: 0000-0002-4106-6255
authors.initials: Q
authors.lastname: Shu
authors.affiliation: Shaoxing Second Hospital, Shaoxing, Zhejiang 312000, China; The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.
authors.forename: Jianguo
authors.identifier: 0000-0002-5053-8525
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D002450:Cell Communication; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011654:Pulmonary Edema / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000378:metabolism
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D053701:Receptors, Interleukin-10; D016753:Interleukin-10