Ageing and Polypharmacy in Mesenchymal Stromal Cells: Metabolic Impact Assessed by Hyperspectral Imaging of Autofluorescence

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dc.contributor.authorChandrasekara, C.M.N.
dc.contributor.authorGemikonakli, G.
dc.contributor.authorMach, J.
dc.contributor.authorSang, R.
dc.contributor.authorAnwer, A.G.
dc.contributor.authorAgha, A.
dc.contributor.authorGoldys, E.M.
dc.contributor.authorHilmer, S.N.
dc.contributor.authorCampbell, J.M.
dc.date.issued2024
dc.description.abstractThe impact of age onmesenchymal stromal cell (MSC) characteristics has been well researched. However, increased age is concomitant with increased prevalence of polypharmacy. This adjustable factor may have further implications for the functionality ofMSCs and the effectiveness of autologousMSC procedures. We applied hyperspectral microscopy of cell autofluorescence—a non-invasive imaging technique used to characterise cytometabolic heterogeneity—to identify changes in the autofluorescence signals of MSCs from (1) young mice, (2) old mice, (3) young mice randomised to receive polypharmacy (9–10 weeks of oral therapeutic doses of simvastatin, metoprolol, oxycodone, oxybutynin and citalopram), and (4) old mice randomised to receive polypharmacy. Principal Component Analysis and Logistic Regression Analysis were used to assess alterations in spectral and associated metabolic characteristics. Modelling demonstrated that cells from young mice receiving polypharmacy had less NAD(P)H and increased porphyrin relative to cells from old control mice, allowing for effective separation of the two groups (AUC of ROC curve > 0.94). Similarly, cells from old polypharmacy mice were accurately separated from those from young controls due to lower levels of NAD(P)H (p < 0.001) and higher porphyrin (p < 0.001), allowing for an extremely accurate logistic regression (AUC of ROC curve = 0.99). This polypharmacy regimenmay have amore profound impact onMSCs than ageing, and can simultaneously reduce optical redox ratio (ORR) and increase porphyrin levels. This has implications for the use of autologousMSCs for older patients with chronic disease.
dc.description.statementofresponsibilityChandrasekara M. N. Chandrasekara, Gizem Gemikonakli, John Mach, Rui Sang, Ayad G. Anwer, Adnan Agha, Ewa M. Goldys, Sarah N. Hilmer, and Jared M. Campbell
dc.identifier.citationInternational Journal of Molecular Sciences, 2024; 25(11):5830-1-5830-16
dc.identifier.doi10.3390/ijms25115830
dc.identifier.issn1661-6596
dc.identifier.issn1422-0067
dc.identifier.orcidCampbell, J.M. [0000-0003-0163-4251]
dc.identifier.urihttps://hdl.handle.net/2440/147942
dc.language.isoen
dc.publisherMDPI AG
dc.relation.granthttp://purl.org/au-research/grants/arc/DP170101863
dc.relation.granthttp://purl.org/au-research/grants/arc/DP210102960
dc.rights© 2024 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 (https://creativecommons.org/licenses/by/4.0/).
dc.source.urihttp://dx.doi.org/10.3390/ijms25115830
dc.subjectmesenchymal stem cell; aging; autofluorescence; non-invasive imaging; spectral microscopy; polypharmacy
dc.subject.meshMesenchymal Stem Cells
dc.subject.meshAnimals
dc.subject.meshMice
dc.subject.meshNADP
dc.subject.meshPolypharmacy
dc.subject.meshAging
dc.subject.meshMale
dc.subject.meshOptical Imaging
dc.titleAgeing and Polypharmacy in Mesenchymal Stromal Cells: Metabolic Impact Assessed by Hyperspectral Imaging of Autofluorescence
dc.typeJournal article
pubs.publication-statusPublished online

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