Frontiers in Immunology (Oct 2022)
Perturbations of mesenchymal stromal cells after allogeneic hematopoietic cell transplantation predispose for bone marrow graft-versus-host-disease
- Thomas Krüger,
- Thomas Krüger,
- Rebekka Wehner,
- Rebekka Wehner,
- Rebekka Wehner,
- Maik Herbig,
- Maik Herbig,
- Maik Herbig,
- Martin Kräter,
- Martin Kräter,
- Michael Kramer,
- Jan Moritz Middeke,
- Friedrich Stölzel,
- Catrin List,
- Katharina Egger-Heidrich,
- Raphael Teipel,
- Uta Oelschlägel,
- Martin Wermke,
- Martin Wermke,
- Helena Jambor,
- Manja Wobus,
- Johannes Schetelig,
- Korinna Jöhrens,
- Torsten Tonn,
- Torsten Tonn,
- Julien Subburayalu,
- Julien Subburayalu,
- Julien Subburayalu,
- Julien Subburayalu,
- Marc Schmitz,
- Marc Schmitz,
- Marc Schmitz,
- Marc Schmitz,
- Martin Bornhauser,
- Martin Bornhauser,
- Martin Bornhauser,
- Martin Bornhauser,
- Malte von Bonin,
- Malte von Bonin
Affiliations
- Thomas Krüger
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Thomas Krüger
- German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Rebekka Wehner
- German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Rebekka Wehner
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Rebekka Wehner
- National Center for Tumor Diseases (NCT), Dresden, Germany
- Maik Herbig
- Max Planck Institute for Science of Light and Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany
- Maik Herbig
- Biotechnology Center, Center for Molecular and Cellular Bioengineering Technical University (TU) Dresden Tatzberg, Dresden, Germany
- Maik Herbig
- Center for Regenerative Therapies (CRTD), Dresden, Germany
- Martin Kräter
- Max Planck Institute for Science of Light and Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany
- Martin Kräter
- Biotechnology Center, Center for Molecular and Cellular Bioengineering Technical University (TU) Dresden Tatzberg, Dresden, Germany
- Michael Kramer
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Jan Moritz Middeke
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Friedrich Stölzel
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Catrin List
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Katharina Egger-Heidrich
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Raphael Teipel
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Uta Oelschlägel
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Martin Wermke
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Martin Wermke
- University Cancer Centrum (UCC), Early Clinical Trial Unit (ECTU), University Hospital Carl Gustav Carus, Dresden, Germany
- Helena Jambor
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Manja Wobus
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Johannes Schetelig
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Korinna Jöhrens
- Institute of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
- Torsten Tonn
- 0Institute of Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Torsten Tonn
- 1German Red Cross Blood Donation Service North-East, Dresden, Germany
- Julien Subburayalu
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Julien Subburayalu
- German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Julien Subburayalu
- Center for Regenerative Therapies (CRTD), Dresden, Germany
- Julien Subburayalu
- 2Mildred Scheel Early Career Center, Medical Faculty, Technische Universität Dresden, Dresden, Germany
- Marc Schmitz
- German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Marc Schmitz
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Marc Schmitz
- National Center for Tumor Diseases (NCT), Dresden, Germany
- Marc Schmitz
- Center for Regenerative Therapies (CRTD), Dresden, Germany
- Martin Bornhauser
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Martin Bornhauser
- German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Martin Bornhauser
- National Center for Tumor Diseases (NCT), Dresden, Germany
- Martin Bornhauser
- Center for Regenerative Therapies (CRTD), Dresden, Germany
- Malte von Bonin
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
- Malte von Bonin
- German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- DOI
- https://doi.org/10.3389/fimmu.2022.1005554
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
- mesenchymal stromal cells
- allogeneic hematopoietic stem cell transplantation
- graft-versus-host-disease
- alloreactivity
- bone marrow niche
