ADRENALINE RUSH: UNLOCKING THE IMPACT ON MSC AND FIBROBLAST PROLIFERATION AND MITOCHONDRIAL DYNAMICS

• Published in: Cytotherapy (Oxford, England) Vol. 26; no. 6; p. S35
• Main Authors: Benavides-Almeida, A., Haro-Vinueza, A., Witt, N., Perez, Á., Peña, J., Hernandez, K., Peñaherrera, S., Tenesaca, D., Mitrani, M., Caicedo, A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.06.2024
• Subjects: Adrenaline; Mitochondria; MSCs; MSCs; Mitochondria; Adrenaline
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2024.03.059

Mesenchymal stem/stromal cells (MSCs) play a vital role in the body's healing and regeneration, responding to stress signals like adrenaline. This response, linked to mitochondrial function, is crucial for cell proliferation and understanding MSCs' role in treating diseases and tissue damage. This study investigates how human MSCs and fibroblasts react to adrenaline, focusing on cell growth, mitochondrial activity, and network dynamics. We analyzed the impact of adrenaline on fibroblasts and MSCs (Fig.1). On day one, we plate 50,000 fibroblasts and MSCs into each well of a P12 plate, using 10% Complete DMEM for fibroblasts and Alpha MEM for MSCs. On the second day, the culture medium was changed to introduce a treatment of 10 µM adrenaline, while the control wells continued with the original medium. This treatment was maintained for different durations: 4h and 24h for mitochondrial DNA (mtDNA) quantification, mitochondrial membrane potential by JC1 (Fig. 1b & 1c) and 48h for assessing cell proliferation (Fig. 1a). On the third day, cells were stained with MitoTracker Red to evaluate mitochondrial dynamics (Fig. 1d & 1e). Quantitative analysis of mitochondrial features such as percentage of the condensed and expanded mitochondria (Fig 1.d), footprint, branch length, and network complexity (Fig. 1 e) were conducted using ImageJ's MiNA (Mitochondrial Network Analysis) plugin. By day four, we count the cells for the proliferation assays. Our results indicate a significant reduction in cell proliferation in both fibroblasts and MSCs post-adrenaline exposure compared to controls (Fig. 1a). No changes were observed in the determination of mtDNA content at 24h and the estimation of mitochondrial membrane potential by JC1 (Fig. 1b). Interestingly, mitochondrial activity, footprint, and network complexity showed no significant alterations in fibroblasts; however, MSCs exhibited a notably larger network post-adrenaline exposure. Branch length analysis revealed significant changes in both cell types. In conclusion, our data suggest that adrenaline exposure influences fibroblast and MSC proliferation and alters mitochondrial network in MSCs regarding length. These findings contribute to a better understanding of cellular responses to stress signals, potentially guiding improved therapeutic strategies.