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With their dying breath

SDF1 (red) calls progenitor cells to endothelial cells (green) lacking oxygen. Gurtner/Macmillan

Cells gasping for air call out to progenitor cells for help, according to results from Daniel Ceradini, Geoffrey Gurtner, and colleagues (NYU School of Medicine, New York, NY).

Stem cells and progenitor cells do not start making new tissue just anywhere—most often, they are recruited to injury sites. The chemokine SDF-1 is known to trigger this recruitment, but what causes injured tissues to make SDF-1 was unclear.

Gurtner's group shows that SDF-1 expression is activated by HIF-1, a transcription factor known to be stabilized at low oxygen levels. Tissues with low oxygen and high SDF-1—either injury sites or bone marrow, where progenitors normally hang out—were hot spots for endothelial progenitor cells (EPCs) carrying the SDF-1 receptor, CXCR4. These EPCs adhered better to endothelial cells expressing SDF-1, and they also migrated toward SDF-1 gradients in vitro. Disruption of SDF-1 interactions with CXCR4 prevented EPC homing and blocked vascular regeneration in mice.

Progenitors for other cell types (neurons, muscle, etc) might also respond to SDF-1, but Gurtner focused on EPCs because new vasculature can both repair and prevent injury. "Endothelial cells downstream of a [partial] blood vessel blockage become hypoxic and make SDF-1," he says. "This marks them like a barcode that says this is an area of injury. Often, nothing cataclysmic happens because new vessels form natural bypasses around the blockage."

HIF-1 was already known to induce sprouting of existing blood vessels through the induction of the growth factor VEGF. But hypoxia and HIF-1 were not known to recruit circulating progenitors.

Reference:

Ceradini, D., et al. 2004. Nat. Med. doi:10.1038/nm1075.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 2428K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?