TY - JOUR
T1 - Bone marrow microenvironment in light-chain amyloidosis
T2 - In vitro expansion and characterization of mesenchymal stromal cells
AU - Valsecchi, Chiara
AU - Croce, Stefania
AU - Maltese, Alice
AU - Montagna, Lorenza
AU - Lenta, Elisa
AU - Nevone, Alice
AU - Girelli, Maria
AU - Milani, Paolo
AU - Bosoni, Tiziana
AU - Massa, Margherita
AU - Abbà, Carlotta
AU - Campanelli, Rita
AU - Ripepi, Jessica
AU - De Silvestri, Annalisa
AU - Carolei, Adriana
AU - Palladini, Giovanni
AU - Zecca, Marco
AU - Nuvolone, Mario
AU - Avanzini, Maria Antonietta
N1 - Funding Information:
Funding: This research was funded by a grant number 80380 to MAA from IRCCS Policlinico S. Matteo, Pavia, Italy, by a grant number GR-2018-12368387 from the Italian Ministry of Health to M.N and by Regione Lombardia, funds POR FESR 2014-2020, Project nr.2526393-Force4Cure.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Bone marrow microenvironment
KW - Immunomodulation
KW - Light-chain amyloidosis
KW - Mesenchymal stromal cells
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U2 - 10.3390/biomedicines9111523
DO - 10.3390/biomedicines9111523
M3 - Article
AN - SCOPUS:85118326602
SN - 2227-9059
VL - 9
JO - Biomedicines
JF - Biomedicines
IS - 11
M1 - 1523
ER -