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Human Bone Marrow Mesenchymal Stromal Cell-Derived CXCL12, IL-6 and GDF-15 and Their Capacity to Support IgG-Secreting Cells in Culture Are Divergently Affected by Doxorubicin

1
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden
2
Division of Paediatric Oncology and Paediatric Surgery, Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, Sweden
3
Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, Sweden
4
Medical Research Council, Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK
5
Division of Paediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 52 Huddinge, Sweden
6
Department of Computational Biology, Institute Pasteur, 75015 Paris, France
*
Author to whom correspondence should be addressed.
Academic Editor: Michèle Sabbah
Hemato 2021, 2(1), 154-166; https://doi.org/10.3390/hemato2010009
Received: 28 January 2021 / Revised: 2 March 2021 / Accepted: 5 March 2021 / Published: 13 March 2021
(This article belongs to the Special Issue Stem Cells and Therapy: A Themed Honorary Issue to Prof. Luc Douay)
Various subsets of bone marrow mesenchymal stromal cells (BM MSCs), including fibroblasts, endothelial, fat and reticular cells, are implicated in the regulation of the hematopoietic microenvironment and the survival of long-lived antibody-secreting cells (ASCs). Nowadays it is widely acknowledged that vaccine-induced protective antibody levels are diminished in adults and children that are treated for hematological cancers. A reason behind this could be damage to the BM MSC niche leading to a diminished pool of ASCs. To this end, we asked whether cell cytotoxic treatment alters the capacity of human BM MSCs to support the survival of ASCs. To investigate how chemotherapy affects soluble factors related to the ASC niche, we profiled a large number of cytokines and chemokines from in vitro-expanded MSCs from healthy donors or children who were undergoing therapy for acute lymphoblastic leukemia (ALL), following exposure to a widely used anthracycline called doxorubicin (Doxo). In addition, we asked if the observed changes in the measured soluble factors after Doxo exposure impacted the ability of the BM niche to support humoral immunity by co-culturing Doxo-exposed BM MSCs with in vitro-differentiated ASCs from healthy blood donors, and selective neutralization of cytokines. Our in vitro results imply that Doxo-induced alterations in BM MSC-derived interleukin 6 (IL-6), CXCL12 and growth and differentiation factor 15 (GDF-15) are not sufficient to disintegrate the support of IgG-producing ASCs by the BM MSC niche, and that serological memory loss may arise during later stages of ALL therapy. View Full-Text
Keywords: human bone marrow mesenchymal stromal cells; anthracycline; plasma cell niche; cytokines; chemokines; antibody-secreting cells human bone marrow mesenchymal stromal cells; anthracycline; plasma cell niche; cytokines; chemokines; antibody-secreting cells
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MDPI and ACS Style

Lasaviciute, G.; Höbinger, A.; Ujvari, D.; Salamon, D.; Yusuf, A.; Sundin, M.; Sverremark-Ekström, E.; Chikhi, R.; Nilsson, A.; Saghafian-Hedengren, S. Human Bone Marrow Mesenchymal Stromal Cell-Derived CXCL12, IL-6 and GDF-15 and Their Capacity to Support IgG-Secreting Cells in Culture Are Divergently Affected by Doxorubicin. Hemato 2021, 2, 154-166. https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2010009

AMA Style

Lasaviciute G, Höbinger A, Ujvari D, Salamon D, Yusuf A, Sundin M, Sverremark-Ekström E, Chikhi R, Nilsson A, Saghafian-Hedengren S. Human Bone Marrow Mesenchymal Stromal Cell-Derived CXCL12, IL-6 and GDF-15 and Their Capacity to Support IgG-Secreting Cells in Culture Are Divergently Affected by Doxorubicin. Hemato. 2021; 2(1):154-166. https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2010009

Chicago/Turabian Style

Lasaviciute, Gintare, Anna Höbinger, Dorina Ujvari, Daniel Salamon, Aisha Yusuf, Mikael Sundin, Eva Sverremark-Ekström, Rayan Chikhi, Anna Nilsson, and Shanie Saghafian-Hedengren. 2021. "Human Bone Marrow Mesenchymal Stromal Cell-Derived CXCL12, IL-6 and GDF-15 and Their Capacity to Support IgG-Secreting Cells in Culture Are Divergently Affected by Doxorubicin" Hemato 2, no. 1: 154-166. https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2010009

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