Progenitor cells and retinal angiogenesis.
Nothing more dramatically captures the imagination of the visually impaired patient or the ophthalmologist treating them than the possibility of rebuilding a damaged retina or vasculature with "stem cells." Stem cells (SC) have been isolated from adult tissues and represent a pool of cells that may serve to facilitate rescue/repair of damaged tissue following injury or stress. We propose a new paradigm to "mature" otherwise immature neovasculature or, better yet, stabilize existing vasculature to hypoxic damage. This may be possible through the use of autologous bone marrow (BM) or cord blood derived hematopoietic SC that selectively target sites of neovascularization and gliosis where they provide vasculo- and neurotrophic effects. We have demonstrated that adult BM contains a population of endothelial and myeloid progenitor cells that can target activated astrocytes, a hallmark of many ocular diseases, and participate in normal developmental, or injury-induced, angiogenesis in the adult. Intravitreal injection of these cells from mice and humans can prevent retinal vascular degeneration ordinarily observed in mouse models of retinal degeneration; this vascular rescue correlates with functional neuronal rescue as well. The use of autologous adult BM derived SC grafts for the treatment of retinal vascular and degenerative diseases represents a novel conceptual approach that may make it possible to "mature" otherwise immature neovasculature, stabilize existing vasculature to hypoxic damage and/or rescue and protect retinal neurons from undergoing apoptosis. Such a therapeutic approach would obviate the need to employ destructive treatment modalities and would facilitate vascularization of ischemic and otherwise damaged retinal tissue.
Friedlander
Martin
M
Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92014, USA. friedlan@scripps.edu
Dorrell
Michael I
MI
Ritter
Matthew R
MR
Marchetti
Valentina
V
Moreno
Stacey K
SK
El-Kalay
Mohammad
M
Bird
Alan C
AC
Banin
Eyal
E
Aguilar
Edith
E
D000328:Adult; D001854:Bone Marrow Cells / Q000502:physiology; D036101:Cord Blood Stem Cell Transplantation; D004730:Endothelium, Vascular / Q000166:cytology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018919:Neovascularization, Physiologic; D012164:Retinal Diseases / Q000503:physiopathology* / Q000628:therapy*; D012171:Retinal Vessels / Q000502:physiology* / Q000503:physiopathology; D012449:Safety; D033581:Stem Cell Transplantation