title: CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect.
abstract: Vascular abnormalities are a common component of eye diseases that often lead to vision loss. Vaso-obliteration is associated with inherited retinal degenerations, since photoreceptor atrophy lowers local metabolic demands and vascular support to those regions is no longer required. Given the degree of neurovascular crosstalk in the retina, it may be possible to use one cell type to rescue another cell type in the face of severe stress, such as hypoxia or genetically encoded cell-specific degenerations. Here, we show that intravitreally injected human endothelial colony-forming cells (ECFCs) that can be isolated and differentiated from cord blood in xeno-free media collect in the vitreous cavity and rescue vaso-obliteration and neurodegeneration in animal models of retinal disease. Furthermore, we determined that a subset of the ECFCs was more effective at anatomically and functionally preventing retinopathy; these cells expressed high levels of CD44, the hyaluronic acid receptor, and IGFBPs (insulin-like growth factor-binding proteins). Injection of cultured media from ECFCs or only recombinant human IGFBPs also rescued the ischemia phenotype. These results help us to understand the mechanism of ECFC-based therapies for ischemic insults and retinal neurodegenerative diseases.
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Sakimoto
authors.affiliation: STEMCELL Technologies, Vancouver, British Columbia, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marchetti
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Edith
authors.initials: E
authors.lastname: Aguilar
authors.affiliation: STEMCELL Technologies, Vancouver, British Columbia, Canada.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Salome
authors.initials: S
authors.lastname: Murinello
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Bucher
authors.affiliation: Lowy Medical Research Institute, La Jolla, California, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Trombley
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Regis
authors.initials: R
authors.lastname: Fallon
authors.affiliation: STEMCELL Technologies, Vancouver, British Columbia, Canada.
authors.forename: Ravenska
authors.initials: R
authors.lastname: Wagey
authors.affiliation: STEMCELL Technologies, Vancouver, British Columbia, Canada.
authors.forename: Carrie
authors.initials: C
authors.lastname: Peters
authors.affiliation: Lowy Medical Research Institute, La Jolla, California, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Scheppke
authors.affiliation: Lowy Medical Research Institute, La Jolla, California, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Westenskow
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Friedlander
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000378:metabolism* / Q000637:transplantation; D005312:Fetal Blood; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D058449:Intravitreal Injections; D007511:Ischemia / Q000473:pathology*; D051379:Mice; D012164:Retinal Diseases / Q000473:pathology*; D055351:Retinal Neurons / Q000473:pathology*; D012171:Retinal Vessels / Q000473:pathology*
chemical_list: D018960:Hyaluronan Receptors; D018969:Insulin-Like Growth Factor Binding Proteins; D006820:Hyaluronic Acid