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

Nat Med. 2002 Sep;8(9):1004-10. doi: 10.1038/nm744. Epub 2002 Jul 29.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / pathology*
  • Bone Marrow Cells*
  • Bone Marrow Transplantation
  • Endothelium, Vascular / pathology
  • Genetic Therapy / methods
  • Mice
  • Mice, Inbred Strains
  • Neovascularization, Pathologic*
  • Retina
  • Retinal Degeneration / pathology
  • Retinal Degeneration / therapy
  • Retinal Vessels / pathology*
  • Transfection