Exosomal Microrna Mir-21-5p As Potential Molecular Entity For Neuroprotective Effects Of Mesenchymal Stromal Cells During Cardiopulmonary Bypass.
Kei Kobayashi, Ankush Bansal, Nemanja Saric, Patrick Hanley, Kazue Hashimoto-Torii, Nobuyuki Ishibashi.
Children's National Medical Center, NW, M7703, DC, USA.
Objective: Our ongoing studies found that mesenchymal stromal cells (MSCs) delivered through cardiopulmonary bypass (CPB) reduce CPB-induced inflammation and caspase activation in the piglet brain. Exosomes derived from MSCs include microRNA (miRNA-ex) that are indicated to play a major role in the effects of MSCs. The goal of the study is to determine therapeutic candidates that account for beneficial effects of MSCs. Methods: The profiling of miRNA-ex was performed post collection from cultured MSCs. miRNA-target analysis was performed using Ingenuity Pathway Analysis (IPA). RNA sequencing was performed in the pre-motor cortex of 3hrs post CPB. Genes were compared with CPB group and CPB+MSC group. Differentially expressed genes (DEG) from the result were compared with miRNA-ex. Results: RNA sequencing identified 204 upregulated and 55 downregulated genes in CPB+MSC group compared with the CPB group. IPA analysis of miRNA-ex showed 155 highly predicted upregulated target genes and 38 highly predicted downregulated target genes, which were all included in the gene sets of DEG. Enriched gene ontology terms include fatty acid beta-oxidation, BAD-BCL-xl complex, and regulation of MAPK cascade. miR-21-5p, a regulator of cell proliferation, migration and apoptosis, was involved in 6 molecular networks as a hub node and highly expressed in exosomes, suggesting that miR-21-5p mediates multifaceted functions of the MSCs during neuroprotection. Conclusions: Our integrated transcriptomic analysis suggests that miR-21-5p may mediate multifaceted functions of the MSCs for neuroprotection during CPB. Identified genes and miRNAs will potentially serve as therapeutic targets for enhancing anti-apoptotic and anti-inflammatory processes in neonatal cardiac surgery.
Back to 2022 Abstracts