Tzng, E. | Search bioRxiv

bioRxiv2024

Dual Mechanism of Action: Exosomes from Human iPSC-Cardiomyocytes and Mesenchymal Stem Cells Restore Injured Myocardium

BackgroundTransplantation of mesenchymal stem cells or induced pluripotent stem cell derived cardiomyocytes improve heart function after myocardial infarction in pre-clinical models. Exosomes are extracellular vesicles, 30-150nm in size, which regulate the paracrine signal of the stem cells. We investigated the functional outcomes and biological effects of exosomes from pure populations of human bone marrow derived mesenchymal stem cells (MSCs) and induced pluripotent stem cell derived cardiomyocytes (iCMs) in a porcine acute myocardial infarction model. MethodsYorkshire swine were subject to proximal left anterior descending artery occlusion with a catheter balloon for 1 hour for ischemia-reperfusion injury. Ten 500ul injections containing 5 x 1011 exosomes isolated from the tissue culture media of iCMs or MSCs were delivered transendocardially into the peri-infarct region. Cardiac function was assessed by magnetic resonance imaging (MRI). Multi-omic analyses were performed in the ex vivo swine peri-infarct specimen to delineate the mechanism of action. ResultsCardiac MRI at weeks 2 and 4 showed significant improvement in heart function in iCM-derived exosomes while MSC-derived exosomes showed a trend towards improvement. A comparative analysis of transcriptomic sequencing of the porcine peri-infarct tissue and Next Generation Sequencing of the exosome cargo confirmed the dual mechanism of action. The marked improvements seen in cardiac function are conferred by miRNA carried by the exosomes, particularly by cardioprotective reduction in metabolism during acute myocardial injury while promoting concurrent cardiomyocyte cell cycle re-entry and proliferation. ConclusionsSignificant reduction in myocardial metabolism and increase in proliferation signal pathways were found in both exosome treatment groups; however, distinct sets of microRNAs were found to underlie the mechanism of action in each population of exosomes.

cell biology↗

bioRxiv2022

Accessibility and Reproducible Research Practices in Cardiovascular Literature

BackgroundSeveral fields have described low reproducibility of scientific research and poor accessibility in research reporting practices. Although previous reports have investigated accessible reporting practices that lead to reproducible research in other fields, to date no study has explored the extent of accessible and reproducible research practices in cardiovascular science literature. MethodsTo study accessibility and reproducibility in cardiovascular research reporting, we screened 400 randomly selected articles published in 2019 in three top cardiovascular science publications: Circulation, the European Heart Journal, and the Journal of the American College of Cardiology (JACC). We screened each paper for accessible and reproducible research practices using a set of accessibility criteria including protocol, materials, data, and analysis script availability, as well as accessibility of the publication itself. We also quantified the consistency of open research practices within and across cardiovascular study types and journal formats. ResultsWe identified that fewer than 2% of cardiovascular research publications provide sufficient resources (materials, methods, data, and analysis scripts) to fully reproduce their studies. After calculating an accessibility score as a measure of the extent to which an articles makes its resources available, we also showed that the level of accessibility varies across study types (p = 2e-16) and across journals (p = 5.9e-13). We further show that there are significant differences in which study types share which resources. We also describe the relationship between accessibility scores and corresponding author nationality. ConclusionAlthough the degree to which reproducible reporting practices are present in publications varies significantly across journals and study types; current cardiovascular science reports frequently do not provide sufficient materials, protocols, data, or analysis information to reproduce a study. In the future, having higher standards of accessibility mandated by either journals or funding bodies will help increase the reproducibility of cardiovascular research. FundingAuthors Gabriel Heckerman, Arely Campos-Melendez, and Chisomaga Ekwueme were supported by an NIH R25 grant from the National Heart Lung and Blood Institute (R25HL147666). Eileen Tzng was supported by an AHA Institutional Training Award fellowship (18UFEL33960207).

scientific communication and education↗