Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency
| Autor: | Maria Ester Bernardo, Mattia Algeri, Daniela Ingo, Fabiola De Mattia, Nadia Starc, Paolo Rossi, Alessandro Aiuti, Giuseppe Palumbo, Immacolata Brigida, Valeria Rossella, Antonella Conforti, Franco Locatelli, Mauro Montanari, Angela Pitisci, Pietro Merli, Luigi Tomao |
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| Přispěvatelé: | Starc, N., Ingo, D., Conforti, A., Rossella, V., Tomao, L., Pitisci, A., De Mattia, F., Brigida, I., Algeri, M., Montanari, M., Palumbo, G., Merli, P., Rossi, P., Aiuti, A., Locatelli, F., Bernardo, M. E. |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Adolescent Cellular differentiation Science T-Lymphocytes chronic granulomatous-disease Wiskott-Aldrich syndrome versus-host disease Bone Marrow Cells Biology Lymphocyte Activation Monocytes Article MSC 03 medical and health sciences Immunophenotyping Chronic granulomatous disease medicine Adipocytes Humans Clonogenic assay Child Severe combined immunodeficiency B-Lymphocytes Multidisciplinary Osteoblasts Stem Cells Mesenchymal stem cell Immunologic Deficiency Syndromes Infant Cell Differentiation Mesenchymal Stem Cells medicine.disease Immunity Innate 3. Good health Toll-Like Receptor 3 Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA Child Preschool Cancer research Medicine Female Bone marrow Stem cell |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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