Table 1.
List of components of the MSC-derived exosome molecular cargo to regulate cardiac repairment published in the recent 5 years.
| Diseases | Component | Type of MSCs | Target cell | Function | Reference |
|---|---|---|---|---|---|
| Cardiac preservation | |||||
| Mouse MI | miR-214 | ADRC | CM | ADRC-derived exosomes inhibited cardiomyocyte cell damage under hypoxia in vitro, decreased infarcted size, and improved cardiac function through miR-214-regulated clathrin endocytosis. | [96] |
| Mouse MI | miR-125b-5p | HcBMSCs | CM | Exosomes from hypoxia-conditioned BMSCs can facilitate cardiac repair and ameliorate CM apoptosis through suppressing the expression of the proapoptotic genes p53 and BAK1. | [79] |
| Mouse MI | miR-125b | BMSCs | NMCM | MSC-derived exosomes protect NMCM from hypoxia and serum deprivation-induced autophagic flux, decreased infarct size, and improved cardiac function via miR-125b-mediated p53-Bnip3 signaling. | [69] |
| Mouse MI | miR-22 | BMSCs | NRCMs | Exosomes from ischemic preconditioned BMSCs resulted in antiapoptotic effect on CMs due to ischemia by targeting Mecp2 and displayed reduced cardiac fibrosis. | [78] |
| Mouse I/R | miR-25-3p | BMSCs | CM | BMSC-derived exosomes protected CMs against oxygen-glucose deprivation-induced apoptosis by directly targeting the proapoptotic genes (FASL and PTEN) and EZH2 to confer cardioprotective effects and suppress inflammation post-I/R injury. | [70] |
| Mouse I/R | miR-221/miR-222 | ADSCs | H9C2 | ADSC-derived exosomes protect H9C2 from H2O2-induced injury and repair cardiac I/R injury via the miR-221/miR-222/PUMA/ETS-1 pathway. | [97] |
| Mouse I/R | miR-221/222 | ADSCs | H9C2 | ADSC-CM attenuates cardiac apoptosis and fibrosis I/R-induced cardiac injury via the microRNA-221/222/PUMA/ETS-1 pathway. | [72] |
| Rat MI | miR-19a | hUC-MSCs | H9C2 | Exosomes secreted by hUC-MSCs protected H9C2 by miR-19a/SOX6-mediated AKT activation and JNK3/caspase-3 inhibition. | [98] |
| Rat MI | miR-126 | ADSCs | H9C2 | miR-126-enhanced ADSC-exosomes prevented myocardial damage by inhibiting apoptosis, inflammation, and fibrosis and increasing angiogenesis. | [74] |
| Rat MI | miR-146a | ADSCs | H9C2 | miR-146a containing exosomes had more effect than the normal exosome treatment group on the suppression of AMI-induced apoptosis, inflammatory response, and fibrosis in an AMI rat model through interacting with the 3′-untranslated region of EGR1. | [71] |
| Rat MI | miR-210 | BMSCs | NRCM | miR-210-overexpressing MSC exosomes exerted myocyte protection by targeting AIFM3 to inhibit NRCM apoptosis and reduce infarct size and improve heart function in the rat MI model. | [75] |
| Rat MI | miR-19a | BMSCs | NRCM | GATA-4-overexpressing MSC-derived exosomes contributed to increased CM survival, reduced CM apoptosis, and preserved mitochondrial membrane potential in CM under a hypoxic environment by targeting PTEN to activate the Akt and ERK signaling. | [43] |
| Rat MI | miR-338 | BMSCs | H9C2 | Exosomes secreted from BMSCs transfected with miR-338 mimic decreased the apoptosis of H9C2 and improved cardiac function by regulating the MAP3K2/JNK signaling pathway. | [77] |
| Rat MI | miR-133 | BMSCs | NRCM | miR-133-overexpressing BMSC-derived exosomes inhibited hypoxia-induced NRCM apoptosis and repressed inflammatory level and the infarct size by targeting snail 1. | [76] |
| Rat MI | miR-29 and miR-24 | BMSCs | H9C2 | BMSC-derived exosomes enriched with miR-29 and miR-24 enhanced cardiac repair by promoting CM proliferation, reducing apoptosis induced by H2O2, and inhibiting fibrosis of fibroblast cell induced by TGF-β. | [17] |
| Rat MI | miR-21 | EnMSCs | NRCM | EnMSCs showed superior cardioprotective effects through antiapoptotic and angiogenic effects by enhancing cell survival through the miR-21/PTEN/Akt pathway. | [73] |
| Rat MI | Circular RNA 0001273 | hUC-MSCs | H9C2 | Circular RNA 0001273 in exosomes of hUC-MSCs inhibited H9C2 apoptosis and promote MI repair. | [81] |
| Rat MI | lncRNA KLF3-AS1 | MSCs | H9C2 | Exosomes secreted from human MSCs inhibited H9C2 pyroptosis and attenuated MI progression through the lncRNA KLF3-AS1/miR-138-5p/Sirt1 pathway. | [80] |
| Rat MI | Sfrp2 | hUC-MSCs | H9C2 | TIMP2-modified hUC-MSC-derived exosomes can inhibit H2O2-induced H9C2 apoptosis and alleviate MI-induced oxidative stress. | [86] |
| Vitro model | miR-144 | BMSCs | H9C2 | BMSC-derived exosomes ameliorated CM apoptosis in hypoxic conditions by delivering miR-144 to recipient cells by targeting the PTEN/AKT pathway. | [99] |
| Vitro model | miR-486-5p | BMSCs | H9C2 | miR-486-5p carried by BMSC-derived exosomes promoted the H9C2 proliferation and rescued H9C2 cells from hypoxia/reoxygenation-induced apoptosis by suppressing PTEN expression and activating the PI3K/AKT signaling pathway. | [100] |
| Vitro model | lncRNA-NEAT1 | hAD-MSCs | hiPSC-derived CM | Exosomes obtained from MIF-pretreated hAD-MSCs exhibited a protective effect on CM cells from hiPSC differentiation through the lncRNA-NEAT1/miR-142-3p/FOXO1 pathway. | [101] |
| Enhanced angiogenesis | |||||
| Mouse MI | miR-132 | BMSCs | HUVEC | BMSC-derived exosomes can both increase tube formation of HUVEC by targeting RASA1 and enhance the neovascularization in the peri-infarct zone. | [82] |
| Mouse MI | miR-210 | BMSCs | HUVEC | miR-210 in BMSC-secreted exosomes improved angiogenesis by increasing the proliferation, migration, and tube formation capacity of HUVECs and contributed to cardiac protection. | [83] |
| Mouse MI | CXCL12, Nrf2 | ADSCs | EPC | The exosomes from SIRT1-overexpressing ADSCs can restore the function of cell migration and tube formation and recruitment of EPCs to the repair area through Nrf2/CXCL12/CXCR7 signaling. | [84] |
| Rat MI | miR-21 | EnMSCs | HUVEC | EnMSCs showed superior cardioprotection through angiogenic effects via the PTEN/Akt pathway. | [73] |
| Rat MI | miR-133a-3p | hUC-MSCs | HUVEC | Exosomes from MIF-engineered hUC-MSCs enhanced proliferation, migration, and angiogenesis. | [85] |
| Rat MI | lncRNA H19 | BMSCs | HUVEC | Exosomes from atorvastatin preconditioned MSCs can regulate the expression of miR-675 and activation of VEGF and intercellular adhesion molecule-1 to promote angiogenesis. | [87] |
| Rat MI | Sfrp2 | hUC-MSCs | HUVEC | TIMP2-modified hUC-MSC-derived exosomes can promote HUVEC proliferation, migration, and tube formation in vitro and angiogenesis in rat MI model. | [86] |
| Rat MI | PDGF-D | hUC-MSCs | HUVEC | Exosomes derived from Akt-modified hUC-MSCs resulted in more effective angiogenesis through PDGF-D secretion. | [88] |
| Limited inflammation | |||||
| Mouse I/R | miRNA-181a | hUCB-MSCs | PBMC | Overexpression of miRNA-181a in hUCB-MSC-derived exosomes suppressed inflammatory response in the PBMCs and promoted Treg cell polarization through targeting c-Fos. | [91] |
| Mouse I/R | miR-182 | BMSCs | Raw264.7 | BMSC-derived exosomes mediated macrophage polarization by targeting toll-like receptor 4. | [90] |
| Mouse MI | LPS-primed exosomes | BMSCs | Raw264.7 | Exosomes obtained from LPS preconditioning BMSCs strongly increased M2 macrophage polarization and attenuated the postinfarction inflammation in the MI model through inhibition of LPS-dependent NF-κB signaling pathway and activation of the AKT1/AKT2 signaling pathway. | [92] |
| Vitro model | miR-10a | AD-MSCs | Naïve T cells | miR-10a-loaded exosomes from AD-MSCs facilitated Th17 and Treg responses while reduced that of Th1 in spleen-derived naïve T cells. | [94] |
| Vitro model | miR-34a, miR-124, and miR-135b | AD-MSCs | THP-1 | Melatonin-stimulated exosomes derived from AD-MSCs promoted M2 macrophage differentiation and exerted superior anti-inflammatory response. | [93] |
| Vitro model | IDO | hUC-MSCs | PBMC | Exosomes from TGF-β and IFN-γ-stimulated hUC-MSCs significantly promoted the transformation of mononuclear cells to Tregs through IDO regulation. | [95] |
| Cardiac remodeling | |||||
| Rat MI | miR-29 and miR-24 | BMSCs | Fibroblast BJ cells | BMSC-secreted exosomes enhanced cardiac repair by transferring miR-29 and miR-24 to fibroblasts. | [17] |
| Rat MI | Sfrp2 | hUC-MSCs | Fibroblast | TIMP2-modified hUC-MSC-derived exosomes decreased TGF-β-induced MMP2, MMP9, and α-SMA secretion in cardiac fibroblasts and inhibit ECM remodeling. | [86] |
| Vitro model | miR-21, miR-23a, miR-125b, and miR-145 | hUC-MSCs | Fibroblast | hUC-MSC-derived exosomes suppressed myofibroblast formation by inhibiting excess α-smooth muscle actin and collagen deposition via the activity of the TGF-β/SMAD2 signaling pathway. | [102] |
AD-MSCs: adipose mesenchymal stem cells; Mecp2: methyl CpG binding protein 2; HUVEC: human umbilical vein endothelial cells; VEGF: vascular endothelial growth factor; EGF: epidermal growth factor; FGF: fibroblast growth factor; VEGF-R2 and VEGF-R3: receptors of vascular endothelial growth factor; MCP-2: monocyte chemoattractant protein 2; MCP-4: monocyte chemoattractant protein 4; PBMC: peripheral blood mononuclear cells; hUC-MSCs: human umbilical cord-derived mesenchymal stem cells; BMSCs: bone marrow mesenchymal stem cells; CTGF: connective tissue growth factor; NRCM: neonatal rat cardiac myocytes; MIF: macrophage migration inhibitory factor; EnMSCs: human endometrium-derived mesenchymal stem cells; PTEN: phosphatase and tensin homolog; ADRC: adipose-derived regenerative cells; CM: cardiomyocytes; I/R: ischemia-reperfusion; ADSCs: adipose-derived stem cells; HcBMSCs: hypoxia-conditioned bone marrow mesenchymal stem cells; AMI: acute myocardial infarction; ADSC-CM: adipose-derived stem cell conditioned medium; NMCM: neonatal mouse cardiomyocytes; hiPSC: human-induced pluripotent stem cell; EGR1: early growth response factor 1; Mecp2: methyl CpG binding protein 2; lncRNA: long noncoding RNA; hUCB-MSCs: human umbilical cord blood-derived MSCs; EPCs: endothelial progenitor cells; PDGF-D: platelet-derived growth factor D; CXCL12: C-X-C motif chemokine 12; Nrf2: nuclear factor E2 related factor 2; Sfrp2: secreted frizzled- (Fz-) related protein 2; TIMP2: tissue matrix metalloproteinase inhibitor 2; MMPs: matrix metalloproteinases; ceRNA: competitive endogenous RNA; LPS: lipopolysaccharide.