title: Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis.
abstract: Adult bone marrow (BM) contains cells capable of differentiating along hematopoietic (Lin(+)) or non-hematopoietic (Lin(-)) lineages. Lin(-) hematopoietic stem cells (HSCs) have recently been shown to contain a population of endothelial precursor cells (EPCs) capable of forming blood vessels. Here we show that intravitreally injected Lin(-) BM cells selectively target retinal astrocytes, cells that serve as a template for both developmental and injury-associated retinal angiogenesis. When Lin(-) BM cells were injected into neonatal mouse eyes, they extensively and stably incorporated into forming retinal vasculature. When EPC-enriched HSCs were injected into the eyes of neonatal rd/rd mice, whose vasculature ordinarily degenerates with age, they rescued and maintained a normal vasculature. In contrast, normal retinal angiogenesis was inhibited when EPCs expressing a potent angiostatic protein were injected. We have demonstrated that Lin(-) BM cells and astrocytes specifically interact with one another during normal angiogenesis and pathological vascular degeneration in the retina. Selective targeting with Lin(-) HSC may be a useful therapeutic approach for the treatment of many ocular diseases.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otani
authors.forename: Karen
authors.initials: K
authors.lastname: Kinder
authors.forename: Karla
authors.initials: K
authors.lastname: Ewalt
authors.forename: Francella J
authors.initials: FJ
authors.lastname: Otero
authors.forename: Paul
authors.initials: P
authors.lastname: Schimmel
authors.forename: Martin
authors.initials: M
authors.lastname: Friedlander
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000473:pathology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D004730:Endothelium, Vascular / Q000473:pathology; D015316:Genetic Therapy / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D009389:Neovascularization, Pathologic; D012160:Retina; D012162:Retinal Degeneration / Q000473:pathology / Q000628:therapy; D012171:Retinal Vessels / Q000473:pathology*; D014162:Transfection