Bone marrow–derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis
A Otani, K Kinder, K Ewalt, FJ Otero, P Schimmel… - Nature medicine, 2002 - nature.com
A Otani, K Kinder, K Ewalt, FJ Otero, P Schimmel, M Friedlander
Nature medicine, 2002•nature.comAdult 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 …
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 …
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.
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