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N. Raschzok Guest Editor - Call for Papers
In: Publications written by: Prof. Dr. Igor M. Sauer
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Pluripotent stem cells have been an important tool for researches in hepatology, starting with mouse embryonic stem cells and transgenesis. Together, with other animal models, they largely contributed to our current knowledge in hepatic cells development and disease modeling. Therefore, with the possibility to manipulate human embryonic stem cells and more recently human induced pluripotent stem cells, there was an existing substratum to study these processes in a human environment, which contributed to the tremendous explosion of the emerging Liver Regenerative Medicine field. The use of such cells in the last few years has been already at the origin of numerous breakthroughs in disease modeling, host-pathogen interactions studies, or liver bioengineering and many are to come.

Investigators are invited to participate in a special issue on „Human Pluripotent Stem Cells in Hepatic Development, Liver Reconstruction and Disease Modeling“ through original research articles at the forefront of this fast pace moving field as well as reviews describing current and forthcoming challenges.

Lead Guest Editor is Karim Si-Tayeb (Institute of the Thorax, Nantes). Guest Editors are Gareth Sullivan (Institute of Basic Medical Sciences, University of Oslo), Robert Schwartz (Weill Cornell Medical College, Cornell University, New York), Nathanael Raschzok (Charité – Universitaetsmedizin Berlin), and Tamir Rashid (King's College London).

Manuscript Due: Friday, 23 January 2015
First Round of Reviews: Friday, 17 April 2015
Publication Date: Friday, 12 June 2015
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

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