Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization.
Adults maintain a reservoir of hematopoietic stem cells that can enter the circulation to reach organs in need of regeneration. We developed a novel model of retinal neovascularization in adult mice to examine the role of hematopoietic stem cells in revascularizing ischemic retinas. Adult mice were durably engrafted with hematopoietic stem cells isolated from transgenic mice expressing green fluorescent protein. We performed serial long-term transplants, to ensure activity arose from self-renewing stem cells, and single hematopoietic stem-cell transplants to show clonality. After durable hematopoietic engraftment was established, retinal ischemia was induced to promote neovascularization. Our results indicate that self-renewing adult hematopoietic stem cells have functional hemangioblast activity, that is, they can clonally differentiate into all hematopoietic cell lineages as well as endothelial cells that revascularize adult retina. We also show that recruitment of endothelial precursors to sites of ischemic injury has a significant role in neovascularization.
Grant
Maria B
MB
Program in Stem Cell Biology, University of Florida, Gainesville, Florida, USA. grantma@pharmacology.ufl.edu
May
W Stratford
WS
Caballero
Sergio
S
Brown
Gary A J
GA
Guthrie
Steven M
SM
Mames
Robert N
RN
Byrne
Barry J
BJ
Vaught
Timothy
T
Spoerri
Polyxenie E
PE
Peck
Ammon B
AB
Scott
Edward W
EW
D000818:Animals; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007511:Ischemia; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D012171:Retinal Vessels / Q000502:physiology*
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins