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

• Published in: Scientific reports 2017-08, Vol.7 (1), p.8153-13, Article 8153
• Main Authors: Starc, Nadia, Ingo, Daniela, Conforti, Antonella, Rossella, Valeria, Tomao, Luigi, Pitisci, Angela, De Mattia, Fabiola, Brigida, Immacolata, Algeri, Mattia, Montanari, Mauro, Palumbo, Giuseppe, Merli, Pietro, Rossi, Paolo, Aiuti, Alessandro, Locatelli, Franco, Bernardo, Maria Ester
• Format: Article
• Language: English
• Subjects: 13; 13/100; 13/21; 13/31; 38; 38/77; 631/250/249/2512; 631/532/2074; Biological analysis; Bone marrow; Chronic granulomatous disease; Dendritic cells; Gene expression; Humanities and Social Sciences; Immunomodulation; Inflammation; Lymphocytes; Lymphocytes B; Mesenchymal stem cells; Mesenchyme; Monocytes; multidisciplinary; Pediatrics; Peripheral blood mononuclear cells; Primary immunodeficiencies; Science; Science (multidisciplinary); Severe combined immunodeficiency; Stromal cells; Toll-like receptors; Wiskott-Aldrich syndrome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-08550-5

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.