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 Blood, 15 March 2007, Vol. 109, No. 6, pp. 2663-2665.
Prepublished online as a Blood First Edition Paper on November 14, 2006; DOI 10.1182/blood-2006-07-033902.

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TRANSPLANTATION

Brief Report

Donor-derived cells and human graft-versus-host disease of the skin

Hideyuki Murata1,2, Anne Janin1,4, Christophe Leboeuf1,2,4, Jean Soulier1,2,5, Eliane Gluckman6, Veronique Meignin1,3, and Gerard Socie1,2,4,6

1 Institut National de la Santé et de la Recherche Médicale (INSERM), U728, Paris, France; 2 Université Paris 7, Paris, France; 3 Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Service de Pathologie, Paris, France; 4 Laboratoire de Recherche Corresondant du CEA (LRC CEA), Paris, France; 5 AP-HP, Hôpital Saint-Louis, Service d'Hématologie Biologique, Paris, France; 6 AP-HP, Hôpital Saint-Louis, Service d'Hématologie Greffe de Moelle, Paris, France

Graft-versus-host disease (GvHD)–induced apoptosis of the skin targets both epidermal keratinocytes and dermal endothelial cells. We studied the donor-versus-recipient origin of GvHD of these target cells in skin of 18 sex-mismatched hematopoietic stem-cell transplant (HSCT) recipients. Combining XY fluorescence in situ hybridization (FISH) and double immunostaining, and further 3D tissue Z-stack analysis, we found keratinocytes and endothelial cells of donor origin, but only in patients with GvHD. Using terminal dUTP nick-end labeling (TUNEL) assay on sister sections, we found a correlation between the numbers of chimeric and apoptotic epidermal and endothelial cells. Moreover, donor-derived cells were more numerous and preferentially distributed in the areas of severe GvHD damage in biopsies performed early in the course of GvHD, whereas they were less numerous and found in the whole epidermis in late biopsies. Because donor-derived cells were found at the site and at the time of maximum tissue damage, they could contribute to epidermal and microvessel repair.


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