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Vox Sang. 2018 Nov;113(8):803-810. doi: 10.1111/vox.12723. Epub 2018 Oct 23.

An alternative for extracorporeal photopheresis: 8-methoxypsoralen and UVA-treated leucocytes from allogeneic donors improve graft-versus-host disease in mice.

Author information

1
Department of Transfusion Medicine, University Medical Center Göttingen, Göttingen, Germany.
2
Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.
3
Department of Experimental Endocrinology, University Medical Center Göttingen, Göttingen, Germany.

Abstract

BACKGROUND AND OBJECTIVE:

Extracorporeal photopheresis (ECP) is an important immune tolerance inducing therapy for graft-versus-host disease (GvHD). However, a sufficient number of ECP cycles cannot be performed in patients with severe GvHD and contraindications for apheresis. Allogeneic sources of leucocytes for use as ECP treatment would be of great benefit. Therefore, this study aimed to test the therapeutic potential of novel sources of leucocytes for ECP.

MATERIALS AND METHODS:

Graft-versus-host disease mice were treated with ECP using therapeutic cells from different allogeneic sources. Splenocytes were incubated with 8-methoxypsoralen (8-MOP), irradiated with UVA light and injected into GvHD mice as a model for ECP.

RESULTS:

The therapy with 8-MOP/UVA-treated cells from healthy mice of the bone marrow transplantation (BMT) donor strain reduced the GvHD symptoms, at least in a model of chronic GvHD. In the acute GvHD model, 8-MOP/UVA-treated cells from the BMT donor or recipient strain did not show significant improvements in GvHD symptoms or survival time. Pre-activation of cells by mixed lymphocyte reactions before 8-MOP/UVA treatment also failed to result in significant differences in survival time or GvHD score. In contrast, ECP with third-party 8-MOP/UVA-treated cells from a HLA-mismatched donor resulted in a mean survival time of 37 days compared to 21 days in the control group.

CONCLUSION:

In our analysis of novel allogeneic leucocyte sources for ECP, we could demonstrate that the source of the 8-MOP/UVA-treated cells is crucial. The underlying immunologic effect of allogeneic 8-MOP/UVA-treated cells needs to be investigated in future studies.

KEYWORDS:

apheresis-therapeutic; apoptosis; cellular therapy; donors; hematopoietic stem cell

PMID:
30353554
DOI:
10.1111/vox.12723
[Indexed for MEDLINE]

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