Mitochondria-Rich Extracellular Vesicles Rescue Patient-Specific Cardiomyocytes From Doxorubicin Injury
| Autor: | Robert Sinclair, Yitian Zeng, Gentaro Ikeda, Ji Hye Jung, Christine Wahlquist, Utkan Demirci, Yunshin Jung, Nathan Bayardo, Adrian P. Gee, Connor O'Brien, Zewen Jiang, Katrin J. Svensson, Elizabeth S. Egan, Evgeniya Vaskova, Michelle R. Santoso, Phillip C. Yang, Ronald M. Witteles, Mark Mercola, Mehmet Ozgun Ozen, Liye Shi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Anthracycline
Cardiomyopathy heart failure MSC mesenchymal stem cell Mitochondrion anthracycline L-EV large extracellular vesicle DZR dexrazoxane ROS reactive oxygen species EV extracellular vesicle medicine MSC-EV mesenchymal stem cell derived extracellular vesicle Doxorubicin MTG MitoTracker Green Original Research MPP+ 1-methyl-4-phenylpyrindinium business.industry Mesenchymal stem cell Cancer RBC red blood cell Patient specific medicine.disease DOX doxorubicin AIC anthracycline induced cardiomyopathy iCM induced cardiomyocyte Oncology Heart failure Cancer research Cardiology and Cardiovascular Medicine business cardiomyopathy S-EV small extracellular vesicle MTDR MitoTracker Deep Red medicine.drug |
| Zdroj: | JACC: CardioOncology |
| ISSN: | 2666-0873 |
| DOI: | 10.1016/j.jaccao.2021.05.006 |
| Popis: | Background Anthracycline-induced cardiomyopathy (AIC) is a significant source of morbidity and mortality in cancer survivors. The role of mesenchymal stem cells (MSCs) in treating AIC was evaluated in the SENECA trial, a Phase 1 National Heart, Lung, and Blood Institute–sponsored study, but the mechanisms underpinning efficacy in human tissue need clarification. Objectives The purpose of this study was to perform an in vitro clinical trial evaluating the efficacy and putative mechanisms of SENECA trial–specific MSCs in treating doxorubicin (DOX) injury, using patient-specific induced pluripotent stem cell–derived cardiomyocytes (iCMs) generated from SENECA patients. Methods Patient-specific iCMs were injured with 1 μmol/L DOX for 24 hours, treated with extracellular vesicles (EVs) from MSCs by either coculture or direct incubation and then assessed for viability and markers of improved cellular physiology. MSC-derived EVs were separated into large extracellular vesicles (L-EVs) (>200 nm) and small EVs ( Central Illustration |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|