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

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2021 Nov 27

PMID 34829752

Authors

Chiara Valsecchi

Stefania Croce

Alice Maltese

Lorenza Montagna

Elisa Lenta

Alice Nevone

Maria Girelli

Paolo Milani

Tiziana Bosoni

Margherita Massa

Carlotta Abba

Rita Campanelli

Jessica Ripepi

Annalisa De Silvestri

Adriana Carolei

Giovanni Palladini

Marco Zecca

Mario Nuvolone

Maria Antonietta Avanzini

Affiliations

Soon will be listed here.

Abstract

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.

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