Ageing and Polypharmacy in Mesenchymal Stromal Cells: Metabolic Impact Assessed by Hyperspectral Imaging of Autofluorescence
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Date
2024
Authors
Chandrasekara, C.M.N.
Gemikonakli, G.
Mach, J.
Sang, R.
Anwer, A.G.
Agha, A.
Goldys, E.M.
Hilmer, S.N.
Campbell, J.M.
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International Journal of Molecular Sciences, 2024; 25(11):5830-1-5830-16
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Chandrasekara M. N. Chandrasekara, Gizem Gemikonakli, John Mach, Rui Sang, Ayad G. Anwer, Adnan Agha, Ewa M. Goldys, Sarah N. Hilmer, and Jared M. Campbell
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Abstract
The 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.
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© 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/).