title: Functional endothelial progenitor cells selectively recruit neurovascular protective monocyte-derived F4/80(+) /Ly6c(+) macrophages in a mouse model of retinal degeneration.
abstract: Retinitis pigmentosa is a group of inherited eye disorders that result in profound vision loss with characteristic retinal neuronal degeneration and vasculature attenuation. In a mouse model of retinitis pigmentosa, endothelial progenitor cells (EPC) from bone marrow rescued the vasculature and photoreceptors. However, the mechanisms and cell types underlying these protective effects were uncertain. We divided EPC, which contribute to angiogenesis, into two subpopulations based on their aldehyde dehydrogenase (ALDH) activity and observed that EPC with low ALDH activity (Alde-Low) had greater neuroprotection and vasoprotection capabilities after injection into the eyes of an rd1 mouse model of retinitis pigmentosa compared with EPC with high ALDH activity (Alde-High). Of note, Alde-Low EPC selectively recruited F4/80(+) /Ly6c(+) monocyte-derived macrophages from bone marrow into retina through CCL2 secretion. In addition, the mRNA levels of CCR2, the neurotrophic factors TGF-β1 and IGF-1, and the anti-inflammatory mediator interleukin-10 were higher in migrated F4/80(+) /Ly6c(+) monocyte-derived macrophages as compared with F4/80(+) /Ly6c(-) resident retinal microglial cells. These results suggest a novel therapeutic approach using EPC to recruit neuroprotective macrophages that delay the progression of neural degenerative disease.
authors.affiliation: Department of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Science; Department of Ophthalmology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Fukuda
authors.forename: Masumi
authors.initials: M
authors.lastname: Nagano
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kimura
authors.forename: Ikki
authors.initials: I
authors.lastname: Tsuboi
authors.forename: Georgina
authors.initials: G
authors.lastname: Salazar
authors.forename: Shinji
authors.initials: S
authors.lastname: Ueno
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.forename: Tilo
authors.initials: T
authors.lastname: Kunath
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Oshika
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohneda
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D000950:Antigens, Ly / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis; D042783:Endothelial Cells / Q000502:physiology; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000502:physiology* / Q000637:transplantation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009410:Nerve Degeneration / Q000517:prevention & control; D012160:Retina / Q000473:pathology; D055351:Retinal Neurons / Q000502:physiology; D012171:Retinal Vessels / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D000950:Antigens, Ly; D018925:Chemokines; C526827:Ly6 protein, mouse; D053773:Transforming Growth Factor beta1; C036763:monocyte-macrophage differentiation antigen; D007334:Insulin-Like Growth Factor I
keywords: Endothelial progenitor cell transplantation; Monocyte derived macrophages; Neurovascular protection; Residual microglia