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Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells
04:23

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The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells

Steven M Guthrie1, Lisa M Curtis, Robert N Mames

  • 1Program in Stem Cell Biology and Regenerative Medicine, University of Florida Shand's Cancer Center, Academic Research Building R4-254, 1600 SW Archer Rd, Gainesville, FL 32610, USA.

Blood
|November 18, 2004
PubMed

We have previously established a model inducing hematopoietic stem cell (HSC) production of circulating endothelial progenitor cells (EPCs) to revascularize ischemic injury in adult mouse retina. The unique vascular environment of the retina results in new blood vessel formation primarily from HSC-derived EPCs. Using mice deficient (-/-) in inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), we show that vessel phenotype resulting from hemangioblast activity can be altered by modulation of the NO/NOS pathway. iNOS-/- or eNOS-/- animals were engrafted with wild-type (WT) HSCs expressing green fluorescence protein (gfp+) and subjected to our adult retinal ischemia model. WT hemangioblast activity in adult iNOS-/- recipients resulted in the formation of highly branched blood vessels of donor origin, which were readily perfused indicating functionality. In contrast, eNOS-/- recipients produced relatively unbranched blood vessels with significant donor contribution that were difficult to perfuse, indicating poor functionality. Furthermore, eNOS-/- chimeras had extensive gfp+ HSC contribution throughout their vasculature without additional injury. This neovascularization, via EPCs derived from the transplanted HSCs, reveals that the NO pathway can modulate EPC activity and plays a critical role in both blood vessel formation in response to injury and normal endothelial cell maintenance.

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