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Copyright ©The Author(s) 2024.
World J Stem Cells. Jul 26, 2024; 16(7): 760-772
Published online Jul 26, 2024. doi: 10.4252/wjsc.v16.i7.760
Table 1 Mesenchymal stem cells treatments for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in vitro
Cell sources
Passage number
Cell models
Biological effects
Rat BM MSCsP3-4HepG2 cellsrMSCs alleviated cellular lipotoxicity and metabolic disturbance, primarily by regulating ER stress and calcium homeostasis via SERCA[34]
Mouse BM MSCsP5-10HepG2 cellsmBMSCs restored disordered glucose and lipid metabolism, as well as mitochondrial dysfunction in T2DM/NAFLD[35]
Human UC MSCs derived miR-24-3pNot reportedPrimary hepatocyteshUC-MSC derived miR-24-3p suppressed lipid accumulation, ROS generation, and inflammatory response through targeting KEAP-1 signaling[37]
Human UC MSCs derived miR-627-5pP3L-02 cellshUC-MSC-derived miR-627-5p improved glucose and lipid metabolism by targeting FTO[39]
Mouse AD MSCs derived miR-223-3pP2 or aboveNCTC1469 cellsmADSC-EV-derived miR-223-3p exhibited suppressive effects on lipid accumulation and liver fibrosis by inhibiting the target gene E2F1[42]
Human MenSCsP2-3L-02/AML12 cellsHepatocyte growth factor secreted by MenSCs in NAFLD promoted hepatic glycogen storage and attenuated lipid accumulation through the downregulation Rnf186[43]
Human UC MSCs derived ExosNot reportedHepG2/AML12 cellshUC-MSC-Exos attenuated steatosis in hepatocytes and inhibited oxidative stress in NASH[45]
Mouse AD MSCsP5-6Murine hepatocyte cell line H2.35mADSCs treatment alleviated lipotoxicity-induced apoptosis in steatotic hepatocytes by activating the Notch signaling pathway[46]
Human UC MSCs derived CMNot reportedL-02 cellshMSC-CM enhanced liver mitochondrial function while reducing inflammation and apoptosis by upregulating SIRT1[50]
Human UC MSCs derived ExosP4-7HepRG cellshUC-MSC-Exos reduced inflammatory cytokines by inducing macrophage anti-inflammatory phenotypes[59]
Human CB MSCs derived Exos with curcuminNot reportedHepG2 cellsMSC-Exos with curcumin improved cell viability and inhibited lipogenesis, while the anti-apoptotic pathway involved the downregulation of ASK1, JNK, and BAX genes[63]
Human UC MSC derived ExosP3-4L-02/AML12 cellsMSC-Exos inhibit lipid accumulation by promoting the β-oxidation of fatty acids and suppressing fatty acid synthesis[64]
Table 2 Mesenchymal stem cells treatments for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in vivo
MSC source
Passage number
Animal models
Other instructions
Biological effect
Mouse CB MSCsP5-8Mouse1 × 106 cells/mouse injected (i.v.) at weeks 21 and 23mMSCs transplantation decreased high-fat-induced weight gain, expansion of subcutaneous adipose tissue, steatosis, lobular inflammation, and liver fibrogenesis[33]
Rat BM MSCsP3-4Rat2 × 106 cells/rat injected (i.v.) at weeks 18 and 20rMSCs administration improved lipid metabolism and insulin sensitivity, and inhibited ER stress in the liver[34]
Mouse BM MSCsP5-10Mouse1 × 107 cells/kg body weight injected (i.v.)mBMSCs restored disordered glucose levels, reduced fat accumulation, and corrected mitochondrial dysfunction in mice with diabetes-associated NAFLD[35]
Human UC MSCsP5Rat1 × 106 cells/rat injected (i.v.) at weeks 1 and 5hUC-MSCs in combination with liraglutide improved glycolipid metabolism, insulin resistance, and liver injury in T2DM/NAFLD rats by downregulating TLR4/NF-κB inflammatory pathway and ameliorating oxidative stress[36]
Human UC MSCs derived miR-24-3pNot reportedMouse120 μg/mouse injected (i.v.) weekly for 16 weekshUC-MSC-derived miR-24-3p alleviated lipid accumulation, inflammation, and oxidative stress in NAFLD[37]
Human UC MSCsP3Mouse1 × 106 cells/mouse injected (i.v.) once a week for 6 weekshUC-MSCs improved glucose homeostasis and lipid metabolism, and alleviated hepatic steatosis and liver damage in obese T2DM/NAFLD mice[38]
Human UC MSCs derived miR-627-5pP3Rat100 μg/rat injected (i.v.) once a week for 2 monthshUC-MSC-derived miR-627-5p improved glucose and lipid metabolism, and alleviated liver damage in NAFLD[39]
Rat AD MSCsP3-15Rat2 × 106 cells/rat injected (p.v.)rADSCs improved liver function and lipid metabolism, thereby exerting hepatoprotective effects[40]
Rat AD MSCsP3 Rat2 × 106 cells/rat injected (p.v.)rADSCs improved liver function; reduced lipid accumulation, oxidative stress, and inflammation; and decelerated the progression of NAFLD in the rat model[41]
Mouse AD MSCs derived miR-223-3pP2 or aboveMouse100 μg/mouse injected (i.v.) twice a week for last 6 weeksmADSC-EV-derived miR-223-3p attenuated lipid accumulation and fibrosis by negatively regulating E2F1 expression[42]
Human MenSCsP2-3Mouse5 × 105 cells/mouse injected (i.v.) at weeks 16, 19, and 22Hepatocyte growth factor secreted by MenSCs in fatty liver diseases promoted hepatic glycogen storage and attenuated lipid accumulation in NAFLD[43]
Human BM MSCsP6-15Mouse(0.9-1) × 106 cells/mouse via splenic injectionhBMSCs reduced hepatic lipid content, inflammation, and fibrosis, as well as restored metabolic and tissue homeostasis, by donating human mitochondria to mouse hepatocytes[44]
Human UC MSCs derived ExosNot reportedMouse100 μg/mouse injected (i.v.) twice a week for final 2 weekshUC-MSC-Exos attenuated steatosis, inflammatory responses, and oxidative stress in hepatocytes via the Nrf2/NQO-1 pathway[45]
Mouse AD MSCsP5-6Mouse1 × 105 cells/mouse via splenic injection twice every 2 weeks for 12 weeksmADSCs reduced apoptosis of steatotic hepatocytes and restored cellular proliferation by activating Notch signaling[46]
Rat BM MSCs/
Rat BM MSCs derived Exos
P4Rat1 × 106 cells/mouse injected (i.v.)/15/30/120 μg/kg body weight injected (i.v.) twice per week for 6 weeksrBMSCs and rBMSC-Exos reduced lipid accumulation, hepatotoxicity, oxidation, and hepatocyte apoptosis, and activated mitochondrial mitophagy[47]
Human AD MSCs/ Human AD MSCs derived EVsP4Mouse1 × 106 cells/mouse injected (i.v.)/ 1.0/2.5/5.0 μg injected (i.v.) at week 12hADSCs or hADSC-EVs exhibited anti-inflammatory and anti-fibrotic effects in the NASH model[49]
Human UC MSCs derived CMNot reportedMouse200 μL cells/mouse injected (i.v.) every 3 days for 2 monthshMSC-CM improved glucose tolerance, insulin sensitivity, and mitochondrial function, and alleviated liver dysfunction, lipid accumulation, inflammation, and apoptosis by upregulating SIRT1[50]
Human BM MSCsNot reportedMouse1 × 107 cells/mouse injected (p.v.)hMSCs decreased the inflammatory cytokines, LDL levels, IR, and oxidative stress in NAFLD with T2DM[51]
Mouse BM MSCsP3Mouse0.5 × 106 cells/mouse injected (i.v.) at weeks 33 and 37mMSCs administration prevented the onset of NASH in obese mice[52]
Murine CB MSCsP5-8Mouse1 × 106 cells/mouse injected (i.v.) at weeks 6 and 7mMSCs reduced weight loss, hepatic lipid peroxidation, steatosis, ballooning, lobular inflammation, and fibrogenesis in NASH[53]
Human BM MSCsNot reportedMouse1.5 × 106 cells/mouse injected (i.v.) at day 42Hepatocyte-like cells derived from hBMSCs attenuated liver lipid accumulation and inflammation, and enhanced the regenerative capacity of the liver in NASH[54]
Human UC MSCsNot reportedMouse1 × 106 cells/mouse injected (i.v.) at week 10hMSCs alleviated hepatic steatosis, inflammation, and fibrosis, and reversed microbiome and metabolome disorders[55]
Uncultured mouse AD MSCsNot reportedMouse1 × 106/7.5 × 105 cells/mouse via splenic injection at weeks 24 and 26u-ADSCs derived from a NASH mouse model and wild-type mice had similar effects in reducing inflammation and fibrosis in NASH[56]
Mouse AD MSCsNot reportedMouse1 × 105 cells/mouse via splenic injected at weeks 4 and 8mADSCs administration prevented the progression of NASH fibrosis by suppressing IL-17-mediated inflammation[57]
Human ESC MSCs derived EVsNot reportedMouse1 and 10 μg/50 μL/mouse (i.p.) every other day for last 4 weekshMSC-EVs increased the number of anti-inflammatory M2 macrophages and suppressed fibrosis in NASH[58]
Human UC MSCs derived ExosP4-7Mouse20 mg/kg body weight injected (i.v.) twice a week for 6 weekshUC-MSC-Exos regulated the anti-inflammatory phenotype of macrophages and reversed PPARα protein expression in liver cells[59]
Human AM MSCs derived EVsNot reportedRat15 μg/kg body weight injected (i.v.) at weeks 3 and 4AMSC-EVs alleviated inflammation and fibrosis in a NASH rat model[60]
Human SHEDs derived CMP8-12Mouse0.5 mL cells/mouse injected (i.v.) once a week from week 10 to 12SHED-CM treatment inhibited liver fibrosis, inflammation, and parenchymal cell apoptosis in NASH[61]
Human CB MSCs derived Exos with curcuminNot reportedMouse15 μg/kg body weight injected (i.v.)Exosomes derived from curcumin-preconditioned MSCs ameliorated NASH, protected against recurrence, and regulated inflammatory response, oxidative stress, and mitochondrial-dependent apoptosis[63]
Human UC MSC derived ExosP3-4Mouse10 mg/kg body weight injected (i.v.) for last 4 weekshUC-MSC-Exos effectively reduced lipid deposition and improved liver function in an NAFLD mouse model via CAMKK1-mediated regulation of lipid homeostasis[64]
Rat AD MSCs stimulated with LPSP3-5Rat1.5 × 106 cells/rat injected (i.v.) at week 8 for 6 weeksADSCs stimulated with LPS showed potential to alleviate NAFLD by reducing the expression of inflammatory genes and the levels of ROS[65]
Human UC MSCsP5Mouse1.5 × 106 cells/mouse injected (i.v.) at week 32hUC-MSCs administration alleviated obesity, improved glucose metabolism, and reduced hepatic steatosis, inflammation, and fibrosis in NASH[66]