Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency

Abstract Mesenchymal stromal cells (MSCs) represent a key component of bone marrow (BM) microenvironment and display immune-regulatory properties. We performed a detailed analysis of biological/functional properties of BM-MSCs derived from 33 pediatric patients affected by primary immune-deficiencie...

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Autores principales:	Nadia Starc, Daniela Ingo, Antonella Conforti, Valeria Rossella, Luigi Tomao, Angela Pitisci, Fabiola De Mattia, Immacolata Brigida, Mattia Algeri, Mauro Montanari, Giuseppe Palumbo, Pietro Merli, Paolo Rossi, Alessandro Aiuti, Franco Locatelli, Maria Ester Bernardo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a8d074e533241b8af7e7686f9f524fc
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spelling	oai:doaj.org-article:6a8d074e533241b8af7e7686f9f524fc2021-12-02T16:07:58ZBiological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency10.1038/s41598-017-08550-52045-2322https://doaj.org/article/6a8d074e533241b8af7e7686f9f524fc2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08550-5https://doaj.org/toc/2045-2322Abstract Mesenchymal stromal cells (MSCs) represent a key component of bone marrow (BM) microenvironment and display immune-regulatory properties. We performed a detailed analysis of biological/functional properties of BM-MSCs derived from 33 pediatric patients affected by primary immune-deficiencies (PID-MSCs): 7 Chronic Granulomatous Disease (CGD), 15 Wiskott-Aldrich Syndrome (WAS), 11 Severe Combined Immunodeficiency (SCID). Results were compared with MSCs from 15 age-matched pediatric healthy-donors (HD-MSCs). Clonogenic and proliferative capacity, differentiation ability, immunophenotype, immunomodulatory properties were analyzed. WB and RT-qPCR for CYBB, WAS and ADA genes were performed. All PID-MSCs displayed clonogenic and proliferative capacity, morphology and immunophenotype comparable with HD-MSCs. PID-MSCs maintained the inhibitory effect on T- and B-lymphocyte proliferation, except for decreased inhibitory ability of SCID-MSCs at MSC:PBMC ratio 1:10. While HD- and CGD-MSCs were able to inhibit monocyte maturation into immature dendritic cells, in SCID- and WAS-MSCs this ability was reduced. After Toll-like Receptor priming, PID-MSCs displayed in vitro an altered gene expression profile of pro- and anti-inflammatory soluble factors. PID-MSCs displayed lower PPARγ levels and WAS- and SCID-MSCs higher levels of key osteogenic markers, as compared with HD-MSCs. Our results indicate that PID-MSCs may be defective in some functional abilities; whether these defects contribute to disease pathophysiology deserves further investigation.Nadia StarcDaniela IngoAntonella ConfortiValeria RossellaLuigi TomaoAngela PitisciFabiola De MattiaImmacolata BrigidaMattia AlgeriMauro MontanariGiuseppe PalumboPietro MerliPaolo RossiAlessandro AiutiFranco LocatelliMaria Ester BernardoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadia Starc Daniela Ingo Antonella Conforti Valeria Rossella Luigi Tomao Angela Pitisci Fabiola De Mattia Immacolata Brigida Mattia Algeri Mauro Montanari Giuseppe Palumbo Pietro Merli Paolo Rossi Alessandro Aiuti Franco Locatelli Maria Ester Bernardo Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency
description	Abstract Mesenchymal stromal cells (MSCs) represent a key component of bone marrow (BM) microenvironment and display immune-regulatory properties. We performed a detailed analysis of biological/functional properties of BM-MSCs derived from 33 pediatric patients affected by primary immune-deficiencies (PID-MSCs): 7 Chronic Granulomatous Disease (CGD), 15 Wiskott-Aldrich Syndrome (WAS), 11 Severe Combined Immunodeficiency (SCID). Results were compared with MSCs from 15 age-matched pediatric healthy-donors (HD-MSCs). Clonogenic and proliferative capacity, differentiation ability, immunophenotype, immunomodulatory properties were analyzed. WB and RT-qPCR for CYBB, WAS and ADA genes were performed. All PID-MSCs displayed clonogenic and proliferative capacity, morphology and immunophenotype comparable with HD-MSCs. PID-MSCs maintained the inhibitory effect on T- and B-lymphocyte proliferation, except for decreased inhibitory ability of SCID-MSCs at MSC:PBMC ratio 1:10. While HD- and CGD-MSCs were able to inhibit monocyte maturation into immature dendritic cells, in SCID- and WAS-MSCs this ability was reduced. After Toll-like Receptor priming, PID-MSCs displayed in vitro an altered gene expression profile of pro- and anti-inflammatory soluble factors. PID-MSCs displayed lower PPARγ levels and WAS- and SCID-MSCs higher levels of key osteogenic markers, as compared with HD-MSCs. Our results indicate that PID-MSCs may be defective in some functional abilities; whether these defects contribute to disease pathophysiology deserves further investigation.
format	article
author	Nadia Starc Daniela Ingo Antonella Conforti Valeria Rossella Luigi Tomao Angela Pitisci Fabiola De Mattia Immacolata Brigida Mattia Algeri Mauro Montanari Giuseppe Palumbo Pietro Merli Paolo Rossi Alessandro Aiuti Franco Locatelli Maria Ester Bernardo
author_facet	Nadia Starc Daniela Ingo Antonella Conforti Valeria Rossella Luigi Tomao Angela Pitisci Fabiola De Mattia Immacolata Brigida Mattia Algeri Mauro Montanari Giuseppe Palumbo Pietro Merli Paolo Rossi Alessandro Aiuti Franco Locatelli Maria Ester Bernardo
author_sort	Nadia Starc
title	Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency
title_short	Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency
title_full	Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency
title_fullStr	Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency
title_full_unstemmed	Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency
title_sort	biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6a8d074e533241b8af7e7686f9f524fc
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Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency

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