1. Novel pre-clinical mouse models for chronic Graft-versus-Host Disease.
- Author
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Verlaat L, Riesner K, Kalupa M, Jung B, Mertlitz S, Schwarz C, Mengwasser J, Fricke C, and Penack O
- Subjects
- Humans, Mice, Animals, Leukocytes, Mononuclear pathology, Transplantation, Homologous adverse effects, Mice, Inbred C57BL, Bronchiolitis Obliterans Syndrome, Graft vs Host Disease
- Abstract
Despite considerable progress in allogeneic hematopoietic cell transplantation (allo-HCT) has been achieved over the past years, chronic Graft-versus-Host Disease (cGvHD) still contributes to high morbidity rates, thus remaining a major hurdle in allo-HCT patients. To understand the complex pathophysiology of cGvHD and to develop refined prophylaxis and treatment strategies, improved pre-clinical models are needed. In this study, we developed two murine cGvHD models, which display high long-term morbidity but low mortality and depict the heterogeneous clinical manifestations of cGvHD seen in patients. We established a haploidentical C57BL/6→B6D2F1 allo-HCT model that uses myeloablative radiation and G-CSF-mobilized splenocytes as stem cell source and a sub-lethally irradiated Xenograft model, which utilizes the transfer of human peripheral blood mononuclear cells (PBMCs) into NOD scid gamma (NSG)-recipients. We characterized both mouse models to exhibit diverse clinical and histopathological signs of human cGvHD as extensive tissue damage, fibrosis/sclerosis, inflammation and B cell infiltration in cGvHD target organs skin, liver, lung and colon and found a decelerated immune cell reconstitution in the late phase after HCT. Our pre-clinical models can help to gain a deeper understanding of the target structures and mechanisms of cGvHD pathology and may enable a more reliable translation of experimental findings into the human setting of allo-HCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Verlaat, Riesner, Kalupa, Jung, Mertlitz, Schwarz, Mengwasser, Fricke and Penack.)
- Published
- 2023
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