The Effect of Graft-Versus-Host Disease on Skin Endothelial and Epithelial Cell Chimerism in Stem-Cell Transplant Recipients

Willemze, Annemiek; Bakker, Astrid C.; Borne, Peter A. von dem; Bajema, Ingeborg M.; Vossen, Jaak M.

doi:10.1097/tp.0b013e31819d340f

Cited by 16 publications

(11 citation statements)

References 26 publications

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“…43 In our study, we found very few donor-derived endothelial cells in the BM, with the exception of one patient, whose microvessels had a higher number of donor-derived endothelial cells. This patient was the only patient in our cohort who lacked an HLA-identical sibling or a matched unrelated donor and therefore received a haploidentical, T cell-depleted allo-HSCT from his mother.…”

Section: Discussionmentioning

confidence: 77%

GVHD after allogeneic haematopoietic SCT for AML: angiogenesis, vascular endothelial growth factor and VEGF receptor expression in the BM

Medinger

Thewis

Bucher

et al. 2012

Bone Marrow Transplant

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There is increasing evidence suggesting that both angiogenesis and endothelial injury are involved in GVHD. To study the dynamics of angiogenesis, we examined 26 patients with AML who had undergone allogeneic haematopoietic SCT. All were in CR and had either acute GVHD (aGVHD) or chronic GVHD (cGVHD). We performed immunohistochemical studies of BM microvessel density (MVD) using Abs against vascular-endothelial (VE)-cadherin, CD34 and CD105, and expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2. At the time of diagnosis, the MVD in AML patients was higher than that in the normal controls, and the MVD decreased after induction chemotherapy. Patients with aGVHD had a significantly higher MVD than patients without aGVHD. Conversely, patients with cGVHD did not have a significantly different MVD. In previous aGVHD, we also found more VEGF þ megakaryocytes. XY FISH in sex-mismatched patients showed that the BM blood vessels consisted mainly of recipient endothelial cells. Taken together, these results suggest that new vessel formation and the VEGF/VEGFR system are involved in aGVHD.

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Section: Discussionmentioning

confidence: 77%

GVHD after allogeneic haematopoietic SCT for AML: angiogenesis, vascular endothelial growth factor and VEGF receptor expression in the BM

Medinger

Thewis

Bucher

et al. 2012

Bone Marrow Transplant

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“…[37][38][39] These studies used a combination of XY FISH and immunostaining in skin or gut biopsies from sex-mismatched female transplant recipients (with male donors). In skin biopsy samples ECs of donor origin were considerably increased in patients with GVHD.…”

Section: Neovascularization During Gvhdmentioning

confidence: 99%

The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation

Penack

Socié

Brink

2011

Blood

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GVHD and tumor relapse are fundamental problems in allogeneic HSCT. Recent research has linked neovascularization to GVHD, tumor growth, and graft-versus-tumor (GVT) activity. Damage of the endothelium by the conditioning regimen provides the initiation stimulus for recruitment of donor-derived endothelial cells and their progenitors. During the early inflammatory phase of GVHD there is considerable neovascularization facilitating migration of inflammatory cells to target organs. In the course of GVHD, however, the vasculature itself becomes a target of alloreactive donor T cells. As a consequence, later stages of GVHD are characterized by fibrosis and rarefaction of blood vessels. Importantly, the inhibition of tumor-neovascularization by activated donor T cells that release antiangiogenic substances contributes to GVT and may be enhanced by pharmacologic inhibition of neovascularization. Furthermore, the therapeutic inhibition of neovascularization may improve immunotherapy for cancer by enhancing leukocyte infiltration in tumor tissue because of normalization of tumor vessels and stimulation of leukocyte-vessel wall interactions. These insights identify important mechanisms underlining the importance of neovascularization for allogeneic immune responses and move therapeutic approaches targeting neovascularization into the spotlight. This perspective covers current knowledge of the role of neovascularization during GVHD as well as GVT and its implications for HSCT.

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“…Two earlier studies, which did not find donor-type endothelial cells in the stromal constituents of bone marrow up to 3 years after HSCT, 29,30 were contrasted by several reports showing endothelial cell chimerism in skin, gut, heart and bone marrow after gender-mismatched HSCT. [14][15][16][17][18]31,32 All these studies used XY in situ hybridization for the detection of donor-derived cells. Reported numbers of donor-type bone marrow-derived endothelial cells after HSCT varied from 2% in non-GVHD-affected skin and gastrointestinal tract up to 40% in the lung.…”

Section: Discussionmentioning

confidence: 99%

“…Strikingly, the maximal percentage of chimeric endothelial cells was 9.5% during the effector phase of acute GVHD, but, after this phase, the proportion of chimeric cells fell to 2%. Furthermore, Willemeze et al 18 recently reported even higher percentages of donorderived endothelial cell chimerism (up to 25% in skin biopsies) related to both repair of damaged endothelium and maintenance of vascular homeostasis; in contrast, skin epithelial cell chimerism (85%) did not seem to correlate with tissue damage.…”

mentioning

confidence: 99%

“…[14][15][16] Furthermore, it was recently suggested that donorderived endothelial cells participate in endothelial repair during the effector phase of acute GVHD, 17 and donorderived endothelial cells were detected in 25% of sexmismatched skin biopsies following HSCT, especially in patients with acute GVHD, and at later time points. 18 Among others, ABH histo-blood group antigens expressed on endothelial cells represent a potential target for GVHD. Allogeneic HSCT is performed across the ABO-blood group barrier in about 30-50% of patients.…”

Section: Introductionmentioning

confidence: 99%

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Persistence of recipient-type endothelium after allogeneic hematopoietic stem cell transplantation

Mueller¹,

Stüssi²,

Yung³

et al. 2010

Haematologica

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The Effect of Graft-Versus-Host Disease on Skin Endothelial and Epithelial Cell Chimerism in Stem-Cell Transplant Recipients

Abstract: From these results, we conclude that donor-derived endothelial cell chimerism results from repair of damaged endothelium and maintenance of vascular homeostasis. In contrast, epithelial cell chimerism follows a more uniform pattern of engraftment, not influenced by tissue damage.

Cited by 16 publications

References 26 publications

GVHD after allogeneic haematopoietic SCT for AML: angiogenesis, vascular endothelial growth factor and VEGF receptor expression in the BM

GVHD after allogeneic haematopoietic SCT for AML: angiogenesis, vascular endothelial growth factor and VEGF receptor expression in the BM

The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation

Persistence of recipient-type endothelium after allogeneic hematopoietic stem cell transplantation

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