title: Interaction of a specific population of human embryonic stem cell-derived progenitor cells with CD11b+ cells ameliorates sepsis-induced lung inflammatory injury.
abstract: Human embryonic stem cells differentiated under mesoderm-inducing conditions have important therapeutic properties in sepsis-induced lung injury in mice. Single cell suspensions obtained from day 7 human embryoid bodies (d7EBs) injected i.v. 1 hour after cecal ligation and puncture significantly reduced lung inflammation and edema as well as production of tumor necrosis factor-α and interferon-γ in lungs compared with controls, whereas interleukin-10 production remained elevated. d7EB cell transplantation also reduced mortality to 50% from 90% in the control group. The protection was ascribed to d7EB cell interaction with lung resident CD11b+ cells, and was correlated with the ability of d7EB cells to reduce it also reduced production of proinflammatory cytokines by CD11+ cells, and to endothelial NO synthase-derived NO by d7EB cells, leading to inhibition of inducible macrophage-type NO synthase activation in CD11b+ cells. The protective progenitor cells were positive for the endothelial and hematopoietic lineage marker angiotensin converting enzyme (ACE). Only the ACE+ fraction modulated the proinflammatory profile of CD11b+ cells and reduced mortality in septic mice. In contrast to the nonprotective ACE-cell fraction, the ACE+ cell fraction also produced NO. These findings suggest that an ACE+ subset of human embryonic stem cell-derived progenitor cells has a highly specialized anti-inflammatory function that ameliorates sepsis-induced lung inflammation and reduces mortality.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Illinois, Chicago 60612, USA.
authors.forename: Sophie P
authors.initials: SP
authors.lastname: Toya
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Bonini
authors.forename: Ignatius
authors.initials: I
authors.lastname: Gomez
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Bachmaier
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D002454:Cell Differentiation; D002469:Cell Separation; D058948:Cell Tracking; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000637:transplantation*; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology / Q000601:surgery*; D018805:Sepsis / Q000150:complications*
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A