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 Blood, 1 May 2004, Vol. 103, No. 9, pp. 3420-3427.
Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-09-3012.

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Submitted September 3, 2003
Accepted January 4, 2004

Adult bone marrow-derived stem cells utilize R-cadherin to target sites of neovascularization in the developing retina

Michael I Dorrell, Atsushi Otani, Edith Aguilar, Stacey K Moreno, and Martin Friedlander*

Cell Biology, The Scripps Research Institute, La Jolla, CA, USA

* Corresponding author; email: friedlan{at}scripps.edu.

Adult bone marrow contains a population of hematopoietic stem cells (HSC) that can give rise to cells capable of targeting sites of neovascularization in the peripheral or retinal vasculature. However, relatively little is known about the mechanism of targeting of these cells to sites of neovascularization. We have analyzed sub-populations of HSC for the expression of a variety of cell surface adhesion molecules and found that R-cadherin, a calcium dependent cell-cell adhesion molecule important for normal retinal endothelial cell guidance, was preferentially expressed by functionally targeting HSC. Pre-incubation of HSC with function blocking anti-R-cadherin antibodies or novel R-cadherin-specific peptide antagonists effectively prevented targeting of bone marrow-derived cells to the developing retinal vasculature in vivo. Whereas control injected HSC targeted to all three normal developing retinal vascular layers, blocking R-cadherin mediated adhesion resulted in mistargeting of the HSC to the normally avascular outer retina. Our results suggest that vascular targeting of bone marrow-derived HSC is dependent on mechanisms similar to those used by endogenous retinal vascular endothelial cells. Thus, R-cadherin antagonists may be useful in the treatment of neovascular diseases in which circulating HSC contribute to abnormal angiogenesis.


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