Periprocedural therapeutics do not impair extracellular mitochondrial viability in transplantation
Year: 2025
Type: article
Abstract: Mitochondrial transplantation is an emerging therapeutic approach for ischemia-reperfusion injury, offering the potential to restore cellular function through the engraftment of extracellular mitochondria. The successful clinical application of this strategy depends on the delivery of metabolically active mitochondria, yet the impact of circulating therapeutic agents on mitochondrial viability remains poorly understood. This study evaluates the effects of five clinically relevant agents commonly used during endovascular treatment of ischemic stroke—alteplase, cefazolin, lidocaine, phenylephrine, and heparinized saline—on extracellular mitochondria using an ex vivo model. Mitochondria were isolated from human skeletal muscle and mouse liver and exposed to these agents at clinically relevant and supra-physiological concentrations. Metabolic activity was assessed using a resazurin reduction assay as an indicator of mitochondrial viability. Even at concentrations up to 8-fold above clinical exposure, none of the agents significantly impaired mitochondrial function. These findings provide critical toxicological data demonstrating the compatibility of commonly used therapeutics with mitochondrial transplantation, supporting the development of safer and more optimized clinical protocols.
Institution: University of Washington
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4410355885