MiRNA Profiles of Extracellular Vesicles Secreted by Mesenchymal Stromal Cells—Can They Predict Potential Off-Target Effects?

Abstract

The cardioprotective properties of extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are currently being investigated in preclinical studies. Although microRNAs (miRNAs) encapsulated in EVs have been identified as one component responsible for the cardioprotective effect of MSCs, their potential off-target effects have not been sufficiently characterized. In the present study, we aimed to investigate the miRNA profile of EVs isolated from MSCs that were derived from cord blood (CB) and adipose tissue (AT). The identified miRNAs were then compared to known targets from the literature to discover possible adverse effects prior to clinical use. Our data show that while many cardioprotective miRNAs such as miR-22-3p, miR-26a-5p, miR-29c-3p, and miR-125b-5p were present in CB- and AT-MSC-derived EVs, a large number of known oncogenic and tumor suppressor miRNAs such as miR-16-5p, miR-23a-3p, and miR-191-5p were also detected. These findings highlight the importance of quality assessment for therapeutically applied EV preparations.

Adipose-Derived Mesenchymal Stromal Cells Treated with Interleukin 1 Beta Produced Chondro-Protective Vesicles Able to Fast Penetrate in Cartilage

“…Of note to envision clinical and off-the-shelf use of ASC-EVs, agreement was observed between the results obtained in the present work using ASCs from local hip fat and those previously published, with ASCs obtained from abdomen liposuction [ 5 ]. In fact, the list of the 100 more expressed EV-embedded miRNA in basal condition identified in the present study showed a 78% of matching with the previously published data of our research group [ 5 ], which in turn showed a 71–73% of agreement with another recently published dataset [ 20 ]. These results reinforce the concept that ASCs contain EVs with a stable miRNA content, regardless of the site of adipose tissue harvest, with a consistent reproducibility among different donors, even with respect to different ages.…”

MiR-125 Family in Cardiovascular and Cerebrovascular Diseases

“…By far, stem cell therapy has been partially applied to the clinical work of cardiovascular and cerebrovascular diseases ( Hu et al, 2011 ). miR-125b-5p was highly expressed in the miRNA profiles of extracellular vesicles isolated from MSCs derived from cord blood and adipose tissues ( Nazari-Shafti et al, 2020 ). This is the basis of MSCs and their vesicles in the treatment of cardiovascular and cerebrovascular diseases.…”

Diverse RNAs in adipose-derived extracellular vesicles and their therapeutic potential

“…In the cardiovascular system, many miRNAs, such as miR-22-3p, miR-29c-3p, miR-26a-5p, and miR-125b-5p, have been found in EV-ASCs and are associated with cardioprotective properties. 114 AMI is considered as one of the most common causes of death throughout the world. 115 Studies have indicated that adipose-derived EVs could act as target RNA-transfected vehicles to mediate AMI-related therapy.…”