Gene expression profiles in mesenchymal stromal cells from bone marrow, adipose tissue and lung tissue of COPD patients and controls.

Autor: Kruk D; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Yeung ACY; Respiratory Bioinformatics and Molecular Biology (RBMB) Group, The University of Technology Sydney, Ultimo, NSW, Australia.; Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia., Faiz A; Respiratory Bioinformatics and Molecular Biology (RBMB) Group, The University of Technology Sydney, Ultimo, NSW, Australia., Ten Hacken NHT; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Timens W; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van Kuppevelt TH; Department of Biochemistry, University of Nijmegen, Radboud University Medical Center, Nijmegen, The Netherlands., Daamen W; Department of Biochemistry, University of Nijmegen, Radboud University Medical Center, Nijmegen, The Netherlands., Hof D; Department of Biochemistry, University of Nijmegen, Radboud University Medical Center, Nijmegen, The Netherlands., Harmsen MC; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, Groningen, The Netherlands., Rojas M; Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, USA., Heijink IH; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, Groningen, The Netherlands. h.i.heijink@umcg.nl.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.i.heijink@umcg.nl.; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.i.heijink@umcg.nl.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2023 Jan 21; Vol. 24 (1), pp. 22. Date of Electronic Publication: 2023 Jan 21.
DOI: 10.1186/s12931-023-02314-8
Abstrakt: Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental models of COPD, but differences between sources may impact on their potential use in therapeutic strategies in patients.
Aim: To assess the transcriptome of lung-derived MSCs (LMSCs), bone marrow-derived MSCs (BM-MSC) and adipose-derived MSCs (AD-MSCs) from COPD patients and non-COPD controls.
Methods: We studied differences in gene expression profiles between the MSC-subtypes, as well as between COPD and control using RNA sequencing (RNA-seq).
Results: We show that besides heterogeneity between donors, MSCs from different sources have strongly divergent gene signatures. The growth factors FGF10 and HGF were predominantly expressed in LMSCs. MSCs from all sources displayed altered expression profiles in COPD, with most pronounced significantly up- and downregulated genes in MSCs from adipose tissue. Pathway analysis revealed that the most differentially expressed genes in COPD-derived AD-MSCs are involved in extracellular matrix (ECM) binding and expression. In LMSCs, the gene that differed most strongly between COPD and control was CSGALNACT1, an ECM modulating gene.
Conclusion: Autologous MSCs from COPD patients display abnormalities with respect to their transcriptome, which were surprisingly most profound in MSCs from extrapulmonary sources. LMSCs may be optimally equipped for lung tissue repair because of the expression of specific growth factor genes.
(© 2023. The Author(s).)
Databáze: MEDLINE
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