title: Differential macrophage polarization promotes tissue remodeling and repair in a model of ischemic retinopathy.
abstract: Diabetic retinopathy is the leading cause of visual loss in individuals under the age of 55. Umbilical cord blood (UCB)-derived myeloid progenitor cells have been shown to decrease neuronal damage associated with ischemia in the central nervous system. In this study we show that UCB-derived CD14(+) progenitor cells provide rescue effects in a mouse model of ischemic retinopathy by promoting physiological angiogenesis and reducing associated inflammation. We use confocal microscopy to trace the fate of injected human UCB-derived CD14(+) cells and PCR with species-specific probes to investigate their gene expression profile before and after injection. Metabolomic analysis measures changes induced by CD14(+) cells. Our results demonstrate that human cells differentiate in vivo into M2 macrophages and induce the polarization of resident M2 macrophages. This leads to stabilization of the ischemia-injured retinal vasculature by modulating the inflammatory response, reducing oxidative stress and apoptosis and promoting tissue repair.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marchetti
authors.forename: Oscar
authors.initials: O
authors.lastname: Yanes
authors.forename: Edith
authors.initials: E
authors.lastname: Aguilar
authors.forename: Matthew
authors.initials: M
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Friedlander
authors.forename: Stacey
authors.initials: S
authors.lastname: Moreno
authors.forename: Kathleen
authors.initials: K
authors.lastname: Storm
authors.forename: Min
authors.initials: M
authors.lastname: Zhan
authors.forename: Samia
authors.initials: S
authors.lastname: Naccache
authors.forename: Glen
authors.initials: G
authors.lastname: Nemerow
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
authors.forename: Martin
authors.initials: M
authors.lastname: Friedlander
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007511:Ischemia / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000473:pathology*; D012171:Retinal Vessels / Q000473:pathology*
chemical_list: D018950:Lipopolysaccharide Receptors