Bone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells

Immunoglobulin light-chain amyloidosis (AL) is caused by misfolded light chains produced by a small B cell clone. Mesenchymal stromal cells (MSCs) have been reported to affect plasma cell behavior. We aimed to characterize bone marrow (BM)-MSCs from AL patients, considering functional aspects, such...

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Autores principales: Chiara Valsecchi, Stefania Croce, Alice Maltese, Lorenza Montagna, Elisa Lenta, Alice Nevone, Maria Girelli, Paolo Milani, Tiziana Bosoni, Margherita Massa, Carlotta Abbà, Rita Campanelli, Jessica Ripepi, Annalisa De Silvestri, Adriana Carolei, Giovanni Palladini, Marco Zecca, Mario Nuvolone, Maria Antonietta Avanzini
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:d9fdc9231c30407f882466b134b89c9b2021-11-25T16:48:32ZBone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells10.3390/biomedicines91115232227-9059https://doaj.org/article/d9fdc9231c30407f882466b134b89c9b2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1523https://doaj.org/toc/2227-9059Immunoglobulin light-chain amyloidosis (AL) is caused by misfolded light chains produced by a small B cell clone. Mesenchymal stromal cells (MSCs) have been reported to affect plasma cell behavior. We aimed to characterize bone marrow (BM)-MSCs from AL patients, considering functional aspects, such as proliferation, differentiation, and immunomodulatory capacities. MSCs were in vitro expanded from the BM of 57 AL patients and 14 healthy donors (HDs). MSC surface markers were analyzed by flow cytometry, osteogenic and adipogenic differentiation capacities were in vitro evaluated, and co-culture experiments were performed in order to investigate MSC immunomodulatory properties towards the ALMC-2 cell line and HD peripheral blood mononuclear cells (PBMCs). AL-MSCs were comparable to HD-MSCs for morphology, immune-phenotype, and differentiation capacities. AL-MSCs showed a reduced proliferation rate, entering senescence at earlier passages than HD-MSCs. The AL-MSC modulatory effect on the plasma-cell line or circulating plasma cells was comparable to that of HD-MSCs. To our knowledge, this is the first study providing a comprehensive characterization of AL-MSCs. It remains to be defined if the observed abnormalities are the consequence of or are involved in the disease pathogenesis. BM microenvironment components in AL may represent the targets for the prevention/treatment of the disease in personalized therapies.Chiara ValsecchiStefania CroceAlice MalteseLorenza MontagnaElisa LentaAlice NevoneMaria GirelliPaolo MilaniTiziana BosoniMargherita MassaCarlotta AbbàRita CampanelliJessica RipepiAnnalisa De SilvestriAdriana CaroleiGiovanni PalladiniMarco ZeccaMario NuvoloneMaria Antonietta AvanziniMDPI AGarticlelight-chain amyloidosismesenchymal stromal cellsbone marrow microenvironmentimmunomodulationBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1523, p 1523 (2021)
institution DOAJ
collection DOAJ
language EN
topic light-chain amyloidosis
mesenchymal stromal cells
bone marrow microenvironment
immunomodulation
Biology (General)
QH301-705.5
spellingShingle light-chain amyloidosis
mesenchymal stromal cells
bone marrow microenvironment
immunomodulation
Biology (General)
QH301-705.5
Chiara Valsecchi
Stefania Croce
Alice Maltese
Lorenza Montagna
Elisa Lenta
Alice Nevone
Maria Girelli
Paolo Milani
Tiziana Bosoni
Margherita Massa
Carlotta Abbà
Rita Campanelli
Jessica Ripepi
Annalisa De Silvestri
Adriana Carolei
Giovanni Palladini
Marco Zecca
Mario Nuvolone
Maria Antonietta Avanzini
Bone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells
description Immunoglobulin light-chain amyloidosis (AL) is caused by misfolded light chains produced by a small B cell clone. Mesenchymal stromal cells (MSCs) have been reported to affect plasma cell behavior. We aimed to characterize bone marrow (BM)-MSCs from AL patients, considering functional aspects, such as proliferation, differentiation, and immunomodulatory capacities. MSCs were in vitro expanded from the BM of 57 AL patients and 14 healthy donors (HDs). MSC surface markers were analyzed by flow cytometry, osteogenic and adipogenic differentiation capacities were in vitro evaluated, and co-culture experiments were performed in order to investigate MSC immunomodulatory properties towards the ALMC-2 cell line and HD peripheral blood mononuclear cells (PBMCs). AL-MSCs were comparable to HD-MSCs for morphology, immune-phenotype, and differentiation capacities. AL-MSCs showed a reduced proliferation rate, entering senescence at earlier passages than HD-MSCs. The AL-MSC modulatory effect on the plasma-cell line or circulating plasma cells was comparable to that of HD-MSCs. To our knowledge, this is the first study providing a comprehensive characterization of AL-MSCs. It remains to be defined if the observed abnormalities are the consequence of or are involved in the disease pathogenesis. BM microenvironment components in AL may represent the targets for the prevention/treatment of the disease in personalized therapies.
format article
author Chiara Valsecchi
Stefania Croce
Alice Maltese
Lorenza Montagna
Elisa Lenta
Alice Nevone
Maria Girelli
Paolo Milani
Tiziana Bosoni
Margherita Massa
Carlotta Abbà
Rita Campanelli
Jessica Ripepi
Annalisa De Silvestri
Adriana Carolei
Giovanni Palladini
Marco Zecca
Mario Nuvolone
Maria Antonietta Avanzini
author_facet Chiara Valsecchi
Stefania Croce
Alice Maltese
Lorenza Montagna
Elisa Lenta
Alice Nevone
Maria Girelli
Paolo Milani
Tiziana Bosoni
Margherita Massa
Carlotta Abbà
Rita Campanelli
Jessica Ripepi
Annalisa De Silvestri
Adriana Carolei
Giovanni Palladini
Marco Zecca
Mario Nuvolone
Maria Antonietta Avanzini
author_sort Chiara Valsecchi
title Bone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells
title_short Bone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells
title_full Bone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells
title_fullStr Bone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells
title_full_unstemmed Bone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells
title_sort bone marrow microenvironment in light-chain amyloidosis: in vitro expansion and characterization of mesenchymal stromal cells
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/d9fdc9231c30407f882466b134b89c9b
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