期刊
NATURE MEDICINE
卷 8, 期 9, 页码 1004-1010出版社
NATURE AMERICA INC
DOI: 10.1038/nm744
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资金
- NCI NIH HHS [CA92577] Funding Source: Medline
- NEI NIH HHS [EY12598, EY11254, EY12599] Funding Source: Medline
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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