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Perturbations of mesenchymal stromal cells after allogeneic hematopoietic cell transplantation predispose for bone marrow graft-versus-host-disease

Functional impairment of the bone marrow (BM) niche has been suggested as a major reason for prolonged cytopenia and secondary graft failure after allogeneic hematopoietic cell transplantation (alloHCT). Because mesenchymal stromal cells (MSCs) serve as multipotent progenitors for several niche comp...

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Main Authors: Krüger, Thomas (Author) , Wehner, Rebekka (Author) , Herbig, Maik (Author) , Kräter, Martin (Author) , Kramer, Michael (Author) , Middeke, Jan Moritz (Author) , Stölzel, Friedrich (Author) , List, Catrin (Author) , Egger-Heidrich, Katharina (Author) , Teipel, Raphael (Author) , Oelschlägel, Uta (Author) , Wermke, Martin (Author) , Jambor, Helena (Author) , Wobus, Manja (Author) , Schetelig, Johannes (Author) , Jöhrens, Korinna (Author) , Tonn, Torsten (Author) , Subburayalu, Julien (Author) , Schmitz, Marc (Author) , Bornhäuser, Martin (Author) , Bonin, Malte von (Author)
Format: Article (Journal)
Language:English
Published: 12 October 2022
In: Frontiers in immunology
Year: 2022, Volume: 13, Pages: 1-14
ISSN:1664-3224
Online Access:Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1005554
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Author Notes:Thomas Krüger, Rebekka Wehner, Maik Herbig, Martin Kräter, Michael Kramer, Jan Moritz Middeke, Friedrich Stölzel, Catrin List, Katharina Egger-Heidrich, Raphael Teipel, Uta Oelschlägel, Martin Wermke, Helena Jambor, Manja Wobus, Johannes Schetelig, Korinna Jöhrens, Torsten Tonn, Julien Subburayalu, Marc Schmitz, Martin Bornhauser and Malte von Bonin
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Summary:Functional impairment of the bone marrow (BM) niche has been suggested as a major reason for prolonged cytopenia and secondary graft failure after allogeneic hematopoietic cell transplantation (alloHCT). Because mesenchymal stromal cells (MSCs) serve as multipotent progenitors for several niche components in the BM, they might play a key role in this process. We used collagenase digested trephine biopsies to directly quantify MSCs in 73 patients before (n = 18) and/or after alloHCT (n = 65). For the first time, we demonstrate that acute graft-versus-host disease (aGvHD, n = 39) is associated with a significant decrease in MSC numbers. MSC reduction can be observed even before the clinical onset of aGvHD (n = 10). Assessing MSCs instantly after biopsy collection revealed phenotypic and functional differences depending on the occurrence of aGvHD. These differences vanished during ex vivo expansion. The MSC endotypes observed revealed an enhanced population of donor-derived classical dendritic cells type 1 and alloreactive T cells as the causing agent for compartmental inflammation and MSC damage before clinical onset of aGvHD was ascertained. In conclusion, MSCs endotypes may constitute a predisposing conductor of alloreactivity after alloHCT preceding the clinical diagnosis of aGvHD.
Item Description:Gesehen am 15.12.2022
Physical Description:Online Resource
ISSN:1664-3224

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