Abstract
Extracellular vesicles (EVs) derived from stem /progenitor cells harbor immense potential to promote cardiomyocyte survival and neovascularization, and to mitigate ischemic injury. However, EVs’ parental stem/progenitor cells showed modest benefits in clinical trials, suggesting autologous stem cell/EV quality might have been altered by stimuli associated with the co-morbidities such as hyperglycemia associated with diabetes. Hyperglycemia is a characteristic of diabetes and a major driving factor in cardiovascular disease. The functional role of stem/progenitor cell-derived EVs and the molecular signature of their secreted EV cargo under hyperglycemic conditions remain elusive. Therefore, we hypothesized that hyperglycemic stress causes transcriptome changes in stem/progenitor cell-derived EVs that may compromise their reparative function. In this study, we performed an unbiased analysis of EV transcriptome signatures from 3 different stem/progenitor cell types by RNA sequencing. The analysis revealed differential expression of a variety of RNA species in EVs. Specifically, we identified 241 common-dysregulated mRNAs, 21 ncRNAs, and 16 miRNAs in three stem cell-derived EVs. Gene Ontology revealed that potential function of common mRNAs mostly involved in metabolism and transcriptional regulation. This study provides potential candidates for preventing the adverse effects of hyperglycemia-induced stem/progenitor cell-derived EV dysfunction, and reference data for future biological studies and application of stem/progenitor cell-derived EVs.
Highlights
Stem/progenitor cell-based therapy has shown great promise in the treatment of a variety of diseases including myocardial infarction (MI), both in preclinical and clinical trials [1,2]
cardiac progenitor cells (CPCs) isolated from mouse were stimulated with 25
According to mRNA Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) analysis, we found that gene expression and transcriptional regulation are those of most enriched function
Summary
Stem/progenitor cell-based therapy has shown great promise in the treatment of a variety of diseases including myocardial infarction (MI), both in preclinical and clinical trials [1,2]. Autologous stem cell transplantation exhibits challenges such as low viability, low cell retention, and poor engraftment that lead to limited cardiac repair and regeneration [6,7]. Enhancing the efficacy of stem cell-based therapy is of utmost importance. Recent evidence suggests that stem/progenitor cells secrete paracrine factors which benefit cardiac repair and regeneration post-cardiac injury [8,9]. Recent reports show that EV/exosome therapy is an alternative stem cell-free strategy involved in tissue protection and regeneration post-injury [11,12,13]. EV/exosome quality and production are not static; their activity, components, and function are affected by stem cell origin [14]
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