Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis

• Published in: Nature medicine Vol. 8; no. 9; pp. 1004 - 1010
• Main Authors: Friedlander, Martin, Otani, Atsushi, Kinder, Karen, Ewalt, Karla, Otero, Francella J, Schimmel, Paul
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.09.2002
• Subjects: Angiogenesis; Animals; Animals, Newborn; Astrocytes - pathology; B cells; Biology; Blood vessels; Bone marrow; Bone Marrow Cells; Bone Marrow Transplantation; Endothelium, Vascular - pathology; Eye diseases; Gene therapy; Genetic Therapy - methods; Hematopoietic stem cells; Mice; Mice, Inbred Strains; Neovascularization, Pathologic; Retina; Retinal Degeneration - pathology; Retinal Degeneration - therapy; Retinal Vessels - pathology; Stem cells; Transfection
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm744

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.