Intrinsic type 1 interferon (IFN1) profile of uncultured human bone marrow CD45lowCD271+ multipotential stromal cells (BM-MSCs): the impact of donor age, culture expansion and IFNα and IFNβ stimulation

Ganguly, P, Burska, A, Davis, C, El-Jawhari, JJ ORCID: https://orcid.org/0000-0002-0580-4492, Giannoudis, PV and Jones, E, 2020. Intrinsic type 1 interferon (IFN1) profile of uncultured human bone marrow CD45lowCD271+ multipotential stromal cells (BM-MSCs): the impact of donor age, culture expansion and IFNα and IFNβ stimulation. Biomedicines, 8 (7): 214. ISSN 2227-9059

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Abstract

Skeletal aging is associated with reduced proliferative potential of bone marrow (BM) multipotential stromal cells (MSCs). Recent data suggest the involvement of type 1 interferon (IFN1) signalling in hematopoietic stem cell (HSC) senescence. Considering that BM-HSCs and BM-MSCs share the same BM niche, we investigated IFN1 expression profile in human BM-MSCs in relation to donor age, culture-expansion and IFN1 (α and β) stimulation. Fluorescence-activated cell sorting was used to purify uncultured BM-MSCs from younger (19–41, n = 6) and older (59–89, n = 6) donors based on the CD45lowCD271+ phenotype, and hematopoietic-lineage cells (BM-HLCs, CD45+CD271−) were used as controls. Gene expression was analysed using integrated circuits arrays in sorted fractions as well as cultured/stimulated BM-MSCs and Y201/Y202 immortalised cell lines. IFN1 stimulation led to BM-MSC growth arrest and upregulation of many IFN1-stimulated genes (ISGs), with IFNβ demonstrating stronger effects. Uncultured MSCs were characterised by a moderate-level ISG expression similar to Y201 cells. Age-related changes in ISG expression were negligible in BM-MSCs compared to BM-HLCs, and intracellular reactive oxygen species (ROS) levels in BM-MSCs did not significantly correlate with donor age. Antiaging genes Klotho and SIRT6 correlated with more ISGs in BM-MSCs than in BM-HLCs. In patients with osteoarthritis (OA), BM-MSCs expressed considerably lower levels of several ISGs, indicating that their IFN1 signature is affected in a pathological condition. In summary, BM-MSCs possess homeostatic IFN1 gene expression signature in health, which is sensitive to in vitro culture and external IFN1 stimulation. IFN signalling may facilitate in vivo BM-MSC responses to DNA damage and combating senescence and aberrant immune activation.

Item Type:	Journal article
Publication Title:	Biomedicines
Creators:	Ganguly, P., Burska, A., Davis, C., El-Jawhari, J.J., Giannoudis, P.V. and Jones, E.
Publisher:	MDPI AG
Date:	15 July 2020
Volume:	8
Number:	7
ISSN:	2227-9059
Identifiers:	Number Type 10.3390/biomedicines8070214 DOI 1447470 Other
Rights:	© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Borcherds
Date Added:	23 Jun 2021 09:18
Last Modified:	23 Jun 2021 09:18
URI:	https://irep.ntu.ac.uk/id/eprint/43161

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