PDF(Pubmed)
Abstract：
The impact of age on mesenchymal 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 of MSCs and the effectiveness of autologous MSC 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 regimen may have a more profound impact on MSCs than ageing, and can simultaneously reduce optical redox ratio (ORR) and increase porphyrin levels. This has implications for the use of autologous MSCs for older patients with chronic disease.
摘要：
年龄对间充质基质细胞（MSC）特性的影响已被充分研究。然而,年龄的增加伴随着多药疗法的患病率增加。这种可调整的因素可能对MSC的功能和自体MSC程序的有效性具有进一步的影响。我们应用细胞自发荧光的高光谱显微镜-一种用于表征细胞代谢异质性的非侵入性成像技术-来识别来自（1）年轻小鼠的MSC的自发荧光信号的变化，（2）老老鼠，（3）随机接受复方药的年轻小鼠（9-10周口服治疗剂量的辛伐他汀，美托洛尔,羟考酮,奥昔布宁和西酞普兰），和（4）随机接受多重用药的老年小鼠。主成分分析和Logistic回归分析用于评估光谱和相关代谢特征的改变。建模表明，相对于老年对照小鼠的细胞，接受多药治疗的年轻小鼠的NAD（P）H较少，卟啉增加，允许两组有效分离(ROC曲线AUC>0.94)。同样，由于较低水平的NAD（P）H（p<0.001）和较高的卟啉（p<0.001），因此将老年多药小鼠的细胞与年轻对照组的细胞准确分离，允许极其准确的逻辑回归(ROC曲线的AUC=0.99)。这种多重用药方案对MSC的影响可能比衰老更深远，并且可以同时降低光学氧化还原比（ORR）和增加卟啉水平。这对于将自体MSCs用于患有慢性疾病的老年患者具有意义。
