Introduction
Biological properties of EVs
Definition and origin of EVs
Preparation and characterisation methods of EVs
EVs isolation methods
Differential centrifugation (ultracentrifugation)
Density gradient centrifugation
Ultrafiltration
SEC
Precipitation polymerisation
Immunoaffinity capture (immunoaffinity purification or immunoprecipitation)
Purification methods of EVs
Characterisation of EVs
EVs storage and stability
Applications of MSC-EVs in different models of GI diseases
ALI
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) |
HF
NAFLD
No | Diseases | Title of study | Outcomes | References |
---|---|---|---|---|
1 | NAFLD | Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease via delivering miR-223-3p | Amelioration of NAFLD and dwindling of lipid accumulation and HF via miR-223-3p-mediated E2F1 downregulation | (Niu et al. 2022) |
Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles | Attenuating of NASH via reducing of inflammation and fibrosis | (Watanabe et al. 2020) | ||
Human umbilical cord-derived mesenchymal stem cell-exosomal miR-627-5p ameliorates non-alcoholic fatty liver disease by repressing FTO expression | Improving of glucose and lipid metabolism and alleviating of hepatic damage through miR-627-5p-mediated FTO repressing, thereby ameliorating of NAFLD progression | (Cheng et al. 2021) | ||
Upregulation of miR-96-5p by bone marrow mesenchymal stem cells and their exosomes alleviate non-alcoholic steatohepatitis: Emphasis on caspase-2 signaling inhibition | Upregulation of miR-96-5p that impedes caspase-2 which has a key role in inhibition of hyperlipidaemia, lowering NAFLD, hepatic apoptosis and mitochondrial mitophagy | (El-Derany and AbdelHamid 2021) | ||
Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate experimental non-alcoholic steatohepatitis via Nrf2/NQO-1 pathway | Stimulation of Nrf2/NQO-1 pathway, thus amending of NASH-associated hepatic inflammation, lipid metabolism and oxidative stress | (Kang et al. 2022) | ||
Mesenchymal stem cells-derived exosomal miR-24-3p ameliorates non-alcohol fatty liver disease by targeting Keap-1 | Amending of NAFLD by miR-24-3p delivery, which inhibited metabolic stress-induced oxidative stress, lipid accumulation, and inflammatory response by targeting Keap-1 | (Du et al. 2022) | ||
Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate liver steatosis by promoting fatty acid oxidation and reducing fatty acid synthesis | Preventing of NAFLD via CAMKK1-mediated lipid homoeostasis | (Yang et al. 2023) | ||
Extracellular Vesicles from Amnion-Derived Mesenchymal Stem Cells Ameliorate Hepatic Inflammation and Fibrosis in Rats | Mitigating of NASH by reducing of inflammation and fibrosis | (Ohara et al. 2018) | ||
Human umbilical cord mesenchymal stromal cell-derived exosomes protect against MCD-induced NASH in a mouse model | Alleviating of NASH by augmenting of the anti-inflammatory phenotype of macrophages and upregulating of PPARα protein expression | (Shi et al. 2022) | ||
2 | UC | Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Inflammatory Bowel Disease in Mice | Mitigation of DSS-induced IBD via suppressing of IL-7 expression in macrophages which alleviate inflammatory responses | (Mao et al. 2017) |
Exosomes derived from human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease in mice through ubiquitination | Repairing damaged tissue in the colon and spleen, ameliorating of DSS-induced IBD via inhibition of ubiquitination | (Wu et al. 2018) | ||
HucMSC-exosomes carrying miR-326 inhibit neddylation to relieve inflammatory bowel disease in mice | Inhibition of neddylation process-induced NF-ĸB activation and relieving DSS-induced IBD via miR-326 | (Wang et al. 2020) | ||
hucMSC-derived exosomes attenuate colitis by regulating macrophage pyroptosis via the miR-378a-5p/NLRP3 axis | Improving IBD by inhibiting macrophage pyroptosis via the miR-378a-5p/NLRP3 axis | (Cai et al. 2021) | ||
A novel therapeutic approach for inflammatory bowel disease by exosomes derived from human umbilical cord mesenchymal stem cells to repair intestinal barrier via TSG-6 | Protecting against IBD through restoring intestinal mucosal barrier function and homeostasis of the intestinal immune system via TSG-6 | (Yang et al. 2021) | ||
Olfactory Ecto-Mesenchymal Stem Cell-Derived Exosomes Ameliorate Experimental Colitis via Modulating Th1/Th17 and Treg Cell Responses | Inhibition of T-cells proliferation and differentiation, endorsing of activated T-cells apoptosis as well as inducing of Tregs cells and eventually alleviating of colitis and promoting the repair of damaged intestinal tissues | (Tian et al. 2020) | ||
Extracellular vesicles containing miR-146a attenuate experimental colitis by targeting TRAF6 and IRAK1 | Assuaging of colitis by targeting TRAF6 and IRAK1 expression via miR-146a | (Wu et al. 2019) | ||
Extracellular vesicles derived from bone marrow mesenchymal stem cells attenuate dextran sodium sulfate-induced ulcerative colitis by promoting M2 macrophage polarization | Diminishing of the inflammation in DSS-induced UC by endorsing M2 macrophage polarization via modulating the JAK1/STAT1/STAT6 axis | (Cao et al. 2019) | ||
Adipose-derived mesenchymal stem cell-secreted exosome alleviates dextran sulfate sodium-induced acute colitis by Treg cell induction and inflammatory cytokine reduction | Reduction of Th17 production, and arousing the Treg cells percentage, and thus ameliorating acute colitis | (Heidari et al. 2021) | ||
Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration | Homing to the inflammatory sites of the colorectal tissue, inhibiting inflammatory cell infiltration and colonic inflammation, preventing alterations of colon length and crypt loss, preventing rectal bleeding and reducing histological scores of DAI | (Yu et al. 2021) |