Table 1.
Summary of studies on the role of MSC-EVs in ALI and HF
| No | Diseases | Title of study | Outcomes | References |
|---|---|---|---|---|
| 1 | ALI | Melatonin treatment enhances therapeutic effects of exosomes against acute liver ischemia–reperfusion injury | Further improvement of liver functions, anti-inflammatory, anti-apoptotic and anti-oxidants features | (Sun et al. 2017) |
| Immunosuppressive effect of mesenchymal stem cell-derived exosomes on a concanavalin A-induced liver injury model | Attenuating liver injury through prohibition of apoptosis, improving of the tissue regeneration and expression of anti-inflammatory cytokines as well as increasing numbers of Treg | (Tamura et al. 2016) | ||
| Bone marrow mesenchymal stem cell-derived exosomes attenuate D-GaIN/LPS-induced hepatocyte apoptosis by activating autophagy in vitro | Prohibition of apoptosis and ALI via energising of autophagy markers (LC3II and Beclin-1) | (Zhao et al. 2019) | ||
| Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acetaminophen-induced acute liver failure through activating ERK and IGF-1R/PI3K/AKT signaling pathway | Dwindling of oxidative stress, inflammation and apoptosis via activation of ERK1/2 and PI3K/AKT pathways, thereby attenuating the development of ALI | (Wu et al. 2021) | ||
| HucMSC Exosome-Derived GPX1 is Required for the Recovery of Hepatic Oxidant Injury | Rescuing of the mice from ALI through curtailing of oxidative stress and apoptosis by GPX1 | (Yan et al. 2017) | ||
| Exosomes derived from human umbilical cord blood mesenchymal stem cells improve hepatic ischemia reperfusion injury via delivering miR-1246 | Alleviation of hepatic IR by improving of liver function, and amending of hepatic apoptosis, necrosis and pro-inflammatory mediators via transferring exosomal miR-1246 to dwindle GSK3β-mediated Wnt/β-catenin pathway | (Xie et al. 2019a) | ||
| Exosomal miR-1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance | Protection of hepatocytes from IR injury, modulating of Treg and Th17 cells’ balance to alleviate inflammation via transporting of exosomal miR-1246 targeting IL-6-gp130-STAT3 signaling, which improved the shift of Th17 towards Treg cells | (Xie et al. 2019b) | ||
| Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages | Repairing of the damaged hepatic tissue and reducing of the inflammation via curbing the NLRP3 inflammasome and caspase1 in vivo and in vitro | (Jiang et al. 2019) | ||
| BMSCs-derived miR-223-containing exosomes contribute to liver protection in experimental autoimmune hepatitis | Reduction of inflammation (TNF-α, IL-17A, and IL-1β) and NLRP3/caspase-1 signalling by exosomal miR-223, thereby attenuating the development of autoimmune hepatitis | (Chen et al. 2018) | ||
| Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia–reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response | Amending of liver injury via diminishing of the neutrophils` infiltration, oxidative stress and apoptosis in hepatic tissue | (Yao et al. 2019) | ||
| Extracellular Vesicles Secreted by Human Adipose-derived Stem Cells (hASCs) Improve Survival Rate of Rats with Acute Liver Failure by Releasing lncRNA H19 | Curbing hepatic necrosis, several kinds of inflammation-related cytokines as well as chemokines and inflammatory cell infiltration beside improving of hepatocyte proliferation and anti-apoptotic effects via HGF/ c-Met trajectory | (Jin et al. 2018) | ||
| 2 | HF | Extracellular vesicles-derived miR-150-5p secreted by adipose-derived mesenchymal stem cells inhibits CXCL1 expression to attenuate hepatic fibrosis | Attenuating HF and curbing HSCs activation through the transfer of miR-150-5p resulting in CXCL1 underexpression | (Du et al. 2021) |
| MiR-122 modification enhances the therapeutic efficacy of adipose tissue-derived mesenchymal stem cells against liver fibrosis | Improving the therapeutic efficacy of AMSCs through exosome-mediated miR-122 communication between donor AMSCs and host HSCs, dwindling of HSCs proliferation and collagen maturation, thereby lowering fibrotic alterations in the liver | (Lou et al. 2017) | ||
| Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway | Mitigation of HF by impeding collagen accumulation and HSCs activation via inhibition of Wnt/β-catenin pathway components in vivo and in vitro | (Rong et al. 2019) | ||
| Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation | Stimulating of autophagy and reducing TGF-β1-induced HF by inhibiting the STAT3/Bcl-2/Beclin 1 pathway | (Qu et al. 2017) | ||
| Exosomes derived from mmu_circ_0000623-modified ADSCs prevent liver fibrosis via activating autophagy | Increasing of autophagy and alleviating of HF via exosomal mmu_circ_0000623-mediated activation of miR-125/ATG4D pathway | (Zhu et al. 2020b) | ||
| Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages | Suppressing pro-inflammatory macrophages, promoting anti-inflammatory macrophages and inhibiting of HF progression through miR-148a/KLF6/STAT3 pathway | (Tian et al. 2022) | ||
| Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis | Alleviating of HF through obstructing TGF-β1/Smad axis and epithelial-to-mesenchymal transition | (Li et al. 2013) | ||
| HucMSC-derived exosomes delivered BECN1 induces ferroptosis of hepatic stellate cells via regulating the xCT/GPX4 axis | Mitigation of HF and stimulation of HSCs ferroptosis as well as reduction of GPX4 | (Tan et al. 2022) | ||
| HucMSC-extracellular vesicles downregulated hepatic stellate cell activation and reduced liver injury in S. japonicum-infected mice | Increasing of mice survival and enhancement of liver functions by dwindling of pro-fibrotic genes and inflammatory mediators | (Dong et al. 2020) | ||
| MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem cells | Preventing of HF by inhibiting Smo expression and consequently hedgehog pathway activation via miR-125b | (Hyun et al. 2015) | ||
| SEVs from tonsil-derived mesenchymal stromal cells alleviate activation of hepatic stellate cells and liver fibrosis through miR-486-5p | Preventing of HF by inhibiting Smo expression and consequently hedgehog pathway activation via miR-486-5p | (Kim et al. 2021) | ||
| HMSCs-derived exosome circCDK13 inhibits liver fibrosis by regulating the expression of MFGE8 through miR-17-5p/KAT2B | Inhibition of HF by modulating MFGE8 expression via circCDK13/miR-17-5p/KAT2B axis | (Ma et al. 2023) |
ALI acute liver injury, AKT protein kinase B, ATG4D autophagy related 4D cysteine peptidase, Bcl2 B-cell lymphoma-2, c-Met hepatocyte growth factor receptor, CXCL1 CXC motif chemokine-ligand 1, ERK extracellular regulated protein kinases, EVs extracellular vesicles, GalN galactosamine, GPX glutathione peroxidase, GSK3β glycogen synthase kinase3 beta, hASCs human Adipose-derived Stem Cells, HGF hepatocyte growth factor, HF hepatic fibrosis, HSCs hepatic stellate cells, HucMSCs human umbilical cord mesenchymal stem cells, IGF-1R insulin-like growth factor-1 receptor, IL interleukin, lncRNA human long-chain non-coding RNA, KATB2 lysine Acetyltransferase 2B, KLF6 Kruppel-like factor 6, LPS lipopolysaccharide, MFGE8 milk fat globulin-EGF factor 8, miR microRNA, NLRP3 NOD-like receptor pyrin domain containing 3, PI3K phosphoinositide 3-kinase, Smo smoothened, STAT signal transducer and activator of transcription, TGF-β1 transforming growth factor-beta 1, TH17 T-helper 17, TNF-α tumour necrosis factor-alpha, Treg regulatory T cell, xCT cystine/glutamate antiporter