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
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 t...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-03-01
|
Series: | Hemato |
Subjects: | |
Online Access: | https://www.mdpi.com/2673-6357/2/1/9 |
id |
doaj-7277533e2db84d02a38d647075e58728 |
---|---|
record_format |
Article |
spelling |
doaj-7277533e2db84d02a38d647075e587282021-03-14T00:01:36ZengMDPI AGHemato2673-63572021-03-012915416610.3390/hemato2010009Human 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 DoxorubicinGintare Lasaviciute0Anna Höbinger1Dorina Ujvari2Daniel Salamon3Aisha Yusuf4Mikael Sundin5Eva Sverremark-Ekström6Rayan Chikhi7Anna Nilsson8Shanie Saghafian-Hedengren9Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDivision of Paediatric Oncology and Paediatric Surgery, Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, SwedenDivision of Paediatric Oncology and Paediatric Surgery, Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, SwedenDivision of Paediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 52 Huddinge, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Computational Biology, Institute Pasteur, 75015 Paris, FranceDivision of Paediatric Oncology and Paediatric Surgery, Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, SwedenDivision of Paediatric Oncology and Paediatric Surgery, Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, SwedenVarious 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 <i>in vitro</i>-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 <i>in vitro</i>-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.https://www.mdpi.com/2673-6357/2/1/9human bone marrow mesenchymal stromal cellsanthracyclineplasma cell nichecytokineschemokinesantibody-secreting cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gintare Lasaviciute Anna Höbinger Dorina Ujvari Daniel Salamon Aisha Yusuf Mikael Sundin Eva Sverremark-Ekström Rayan Chikhi Anna Nilsson Shanie Saghafian-Hedengren |
spellingShingle |
Gintare Lasaviciute Anna Höbinger Dorina Ujvari Daniel Salamon Aisha Yusuf Mikael Sundin Eva Sverremark-Ekström Rayan Chikhi Anna Nilsson Shanie Saghafian-Hedengren 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 human bone marrow mesenchymal stromal cells anthracycline plasma cell niche cytokines chemokines antibody-secreting cells |
author_facet |
Gintare Lasaviciute Anna Höbinger Dorina Ujvari Daniel Salamon Aisha Yusuf Mikael Sundin Eva Sverremark-Ekström Rayan Chikhi Anna Nilsson Shanie Saghafian-Hedengren |
author_sort |
Gintare Lasaviciute |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
MDPI AG |
series |
Hemato |
issn |
2673-6357 |
publishDate |
2021-03-01 |
description |
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 <i>in vitro</i>-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 <i>in vitro</i>-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. |
topic |
human bone marrow mesenchymal stromal cells anthracycline plasma cell niche cytokines chemokines antibody-secreting cells |
url |
https://www.mdpi.com/2673-6357/2/1/9 |
work_keys_str_mv |
AT gintarelasaviciute humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT annahobinger humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT dorinaujvari humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT danielsalamon humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT aishayusuf humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT mikaelsundin humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT evasverremarkekstrom humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT rayanchikhi humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT annanilsson humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin AT shaniesaghafianhedengren humanbonemarrowmesenchymalstromalcellderivedcxcl12il6andgdf15andtheircapacitytosupportiggsecretingcellsinculturearedivergentlyaffectedbydoxorubicin |
_version_ |
1724221809072537600 |