Levels of IL-17F and IL-33 correlate with HLA-DR activation in clinical-grade human bone marrow–derived multipotent mesenchymal stromal cell expansion cultures

MARTA GRAU-VORSTER, LUCIANO RODRÍGUEZ, SÍLVIA TORRENTS-ZAPATA, DANIEL VIVAS, MARGARITA CODINACH, MARGARITA BLANCO, IRENE OLIVER-VILA, Joan García López, JOAQUIM VIVES

Producció científica: Contribució a una revistaArticleRecerca

21 Cites (Scopus)

Resum

© 2018 International Society for Cellular Therapy Background aims: Multipotent mesenchymal stromal cell (MSC)-based medicines are extensively investigated for use in regenerative medicine and immunotherapy applications. The International Society for Cell and Gene Therapy (ISCT) proposed a panel of cell surface molecules for MSC identification that includes human leukocyte antigen (HLA)-DR as a negative marker. However, its expression is largely unpredictable despite production under tightly controlled conditions and compliance with current Good Manufacturing Practices. Herein, we report the frequency of HLA-DR expression in 81 batches of clinical grade bone marrow (BM)-derived MSCs and investigated its impact on cell attributes and culture environment. Methods: The levels of 15 cytokines (interleukin [IL]-1β IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon-γ soluble CD40 ligand and tumor necrosis factor-α) were determined in sera supplements and supernatants of BM-MSC cultures. Identity, multipotentiality and immunopotency assays were performed on high (>20% of cells) and low (≤20% of cells) HLA-DR+ cultures. Results: A correlation was found between HLA-DR expression and levels of IL-17F and IL-33. Expression of HLA-DR did neither affect MSC identity, in vitro tri-lineage differentiation potential (into osteogenic, chondrogenic and adipogenic lineages), nor their ability to inhibit the proliferation of stimulated lymphocytes. Discussion: Out of 81 batches of BM-MSCs for autologous use analyzed, only three batches would have passed the ISCT criteria (<2%), whereas 60.5% of batches were compliant with low HLA-DR values (≤20%). Although a cause–effect relationship cannot be drawn, we have provided a better understanding of signaling events and cellular responses in expansion culture conditions relating with HLA-DR expression.
Idioma originalEnglish
Pàgines (de-a)32-40
Nombre de pàgines9
RevistaCytotherapy
Volum21
DOIs
Estat de la publicacióPublicada - 1 de gen. 2019

Fingerprint

Navegar pels temes de recerca de 'Levels of IL-17F and IL-33 correlate with HLA-DR activation in clinical-grade human bone marrow–derived multipotent mesenchymal stromal cell expansion cultures'. Junts formen un fingerprint únic.

Com citar-ho