Mesenchymal stem cell-derived exosomes: a possible therapeutic strategy for repairing heart injuries

Abstract

Mesenchymal stem cells (MSCs) are one of the most potent therapeutic strategies for repairing cardiac injury. It has been shown in the latest studies that MSCs cannot survive in the heart for a long time. Consequently, the exosomes secreted by MSCs may dominate the repair of heart injury and promote the restoration of cardiac cells, vascular proliferation, immune regulation, etc. Based on the current research, the progress of the acting mechanism, application prospects and challenges of exosomes, including non-coding RNA, in repairing cardiac injuries are summarised in this article.

Keywords: exosomes; heart injury; mesenchymal stem cells; miRNA; non-coding RNA.

FIGURE 1

Effect and mechanism of miRNA on MSC-Exos repair myocardial infarction: miR-125b (Xiao et al., 2018), miR-543 (Yang et al., 2021) in BMSC-Exos. miR-1246 (Wang et al., 2021b) in hucMSC-Exos and miR-21-5p (Wang et al., 2017) in EnMSC-Exos. miR-671 in ADMSC-Exos inhibits the expression of target genes (Wang et al., 2021a). miR-199a-3p in BMSC-Exos improves the expression of target genes (Lee et al., 2021). hucMSC-Exos inhibits miR-125b-5p in cardiomyocytes (Wang et al., 2018). The figure was created with BioRender.com.

FIGURE 2

The effect of miRNAs derived from different MSC sources on cardiac I/R injury repair. miR-486-5p and miR-21a-5p (Luther et al., 2018) in BMSC-Exos (Sun et al., 2019). miR-21-5p in EnMSC-Exos (35). miR-221 and miR-222 in ADSC-Exo inhibit the expression of target genes (Lai et al., 2020). miRNA-182 and miR-21-5p in BMSC-Exos promote cardiac function recovery by inducing macrophage polarisation from M1 to M2 (Zhao et al., 2019a; Shen and He, 2021). The figure was created with BioRender.com.

FIGURE 3

Effects of culture methods on MSC-Exos and NC-RNA. LPS upregulated miR-181-5p in BMSC-Exos. Hemin upregulated miR-183-5p in MSC-Exos. Both miR-181-5p and miR-183-5p protect cardiomyocytes by inhibiting the target genes. Hypotreatment upregulated miR-125b-5p (Zhu et al., 2018b), miR-24 (Zhang et al., 2019), miR-98-5p (Zhang et al., 2021) and miR-210 (Zhu et al., 2018a) in BMSC-Exos. miR-98-5p protects cardiac function by inhibiting the target gene, improving PI3K/AKT signaling pathway (Zhang et al., 2021). H/R treatment inhibited miR-29c in BMSC-Exos and impaired the protective effect on the heart of BMSC-Exos (Li et al., 2020a). The figure was created with BioRender.com.

FIGURE 4

The effect of changing the expression of MSC-Exos miRNA on therapeutic effects. miR-126 (Pan et al., 2019b) and miR-132 (Ma et al., 2018) promoted cardiac function by promoting endothelial cells to form blood vessels. miR-338 (Fu et al., 2020), miR-19a (Yu et al., 2015), miR-30e (Pu et al., 2021), miR-129-5p (Wang et al., 2022; Yan et al., 2022), miR-133a (Li et al., 2021b), miR-146a (Pan et al., 2019a), miR-150-5p (Wu et al., 2021), miR-183-5p (Mao et al., 2022), miR-182-5p (Yue et al., 2022), miR-185 (Li et al., 2020b) and miR-96 (Lei et al., 2021) promote cardiac function recovery by inhibiting the target gene. miR-301 (Li et al., 2019) promoted the recovery of cardiac function by inhibiting apoptosis. The figure was created with BioRender.com.

FIGURE 5

The role of lncRNAs in MSC-Exos in the repair of cardiac injury. lncRNA-H19 plays a role in promoting endothelial cell angiogenesis (Huang et al., 2020). lncRNA-MALAT1 (Xia et al., 2020), KLF3-AS1 (Mao et al., 2019), HCP5(Li et al., 2021a), NEAT1 (Chen et al., 2020), UCA1 (Sun et al., 2020) and Mir9-3 (Zhang et al., 2022) protect cardiac function by inhibiting the expression of target genes. The figure was created with BioRender.com.