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, 2002nature.com
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 …
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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