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J Invest Dermatol. 2016 Feb;136(2):497-506. doi: 10.1016/j.jid.2015.11.005. Epub 2015 Nov 18.

Delayed Healing of Sickle Cell Ulcers Is due to Impaired Angiogenesis and CXCL12 Secretion in Skin Wounds.

Author information

1
Progenitors and Endothelial Cells During and After Pregnancy Laboratory, INSERM UMR_S 938, Centre de Recherche, St. Antoine, Paris, France; UPMC-Université Paris 6, Paris, France.
2
Progenitors and Endothelial Cells During and After Pregnancy Laboratory, INSERM UMR_S 938, Centre de Recherche, St. Antoine, Paris, France; UPMC-Université Paris 6, Paris, France; Department of Dermatology, American University of Beirut Medical Centre, Beirut, Lebanon; Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
3
Faculty of Medicine, Université Paris Descartes-Paris 5, Paris, France.
4
Progenitors and Endothelial Cells During and After Pregnancy Laboratory, INSERM UMR_S 938, Centre de Recherche, St. Antoine, Paris, France.
5
Paris Center for Cardiovascular Research, INSERM UMRS-970, Paris, France.
6
Progenitors and Endothelial Cells During and After Pregnancy Laboratory, INSERM UMR_S 938, Centre de Recherche, St. Antoine, Paris, France; Faculty of Medicine, Université Paris Descartes-Paris 5, Paris, France; Department of Dermatology, Hôpital Cochin-Tarnier, Paris, France. Electronic address: selim.aractingi@gmail.com.

Abstract

Leg ulcers are a major complication of sickle cell disease that occur in 2.5-40% of patients. Leg ulcers are responsible for frequent complications because they are often long-lasting and are highly resistant to therapy. Although their occurrence is associated with hyperhemolysis, the mechanisms underlying sickle cell ulcers remain poorly understood. In this study, we show that skin wound healing is severely altered in old SAD sickle cell mice but is normal in young animals, consistent with reports in humans. Alterations of wound healing were associated with impaired blood and lymphatic angiogenesis in the wound beds and poor endothelial progenitor cell mobilization from the bone marrow. CXCL12 secretion by keratinocytes and inflammatory cells was low in the wounds of SAD mice. Local therapy with endothelial progenitor cells or recombinant CXCL12 injections restored wound angiogenesis and rescued the healing defect together with mobilization of circulating endothelial progenitor cells. To our knowledge, this is a previously unreported study of the cellular and molecular mechanisms of sickle cell ulcers in a murine model that provides promising therapeutic perspectives for clinical trials.

PMID:
26967481
DOI:
10.1016/j.jid.2015.11.005
[Indexed for MEDLINE]
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