Table 1 Preclinical trials of mesenchymal stem cell therapy in animal models of LPS-induced inflammatory diseases
Animal model | LPS delivery Route | MSCs used | Mechanism | Main findings | Year | References |
|---|---|---|---|---|---|---|
ALI、ARDS | intratracheal injection | bone marrow-derived MSCs | exosome | MiR-23a-3p transmitted by MSC-exosome regulates the ubiquitination of IKKβ and MiR-182-5p transmitted by MSC-exosomes reverses EMT process | 2020 | [60] |
intratracheal injection | adipose-derived MSCs | transfer mitochondrial | AdMSC-Exos transfers mitochondria to macrophages, alleviating lung inflammation and injury | 2022 | [62] | |
tracheal instillation | bone marrow-derived MSCs | exosome | BM-MSC-exosomes down-regulate transforming growth factor-β receptor 1 by delivering miR-130b-3p and reduce alveolar cell apoptosis to alleviate LPS-induced ALI in mice | 2022 | [61] | |
intratracheally nebulization | umbilical cord-derived MSCs | activate the IL-17, JAK-STAT, NF-κB, and TNF-α signaling pathways | MSCs reduce inflammation, inhibit pulmonary fibrosis, and improve lung ventilation | 2022 | [63] | |
Liver failure | intraperitoneal injections | human amnioticl MSCs | HGF/c-Met Signal path | Hypoxia-mesenchymal stem cells can reduce inflammatory cell infiltration, inhibit liver cell apoptosis, and improve homing rate | 2024 | [66] |
Acute pancreatitis | intraperitoneal injection | adipose-derived MSCs | paracrine | TSG-6 secreted by AD-MSCs protects PAC in SAP model mice by inhibiting ER stress and inflammatory response | 2018 | [68] |
Intestinal barrier dysfunction | intraperitoneal injection | adipose-derived MSCs | immunomodulation | By preventing the infiltration of inflammatory cells in the intestines and downregulating the Th1 inflammatory response while upregulating the Th2 response, intestinal tissue damage is protected in GI colitis and LPS-induced sepsis | 2009 | [110] |
gavage feeding + hypoxia + oral | amniotic fluid stem cell | COX-2 dependent mechanism | AFS can modulate stromal cells expressing COX-2, reduce intestinal inflammation and intestinal epithelial cell apoptosis in NEC rats | 2014 | [70] | |
Interstitial cystitis | intravesical instillation | M-MSC | combination therapy with M-MSC and NAC effectively protect urothelium and decrease mast cell infiltration and apoptosis, improving urinary dysfunction | 2019 | [71] | |
intravesical instillation | urine-derived stem cells | USCs restore bladder function by suppressing oxidative stress, inflammatory response, and apoptosis | 2017 | [72] | ||
Acute kidney injury | intraperitoneal injection | adipose-derived MSCs | exosome | ADSC-derived exosomal circVMA21 alleviates LPS-induced AKI by targeting miR-16-5p, thereby inhibiting apoptosis, inflammation, and aerobic glycolysis | 2023 | [75] |
intraperitoneal injection | renal MSCs | paracrine | EPC-MSC promotes macrophage polarization and reduces levels of pro-inflammatory cytokines | 2015 | [76] | |
Neurological disease | substantia nigra injection | bone marrow-derived MSCs | neuronutrition | intra-nigral LPS administration induced localized microgliosis and GDNF-MSC treatment provided local neuroprotection of dopaminergic terminals | 2015 | [80] |
intraperitoneal injection | bone marrow-derived MSCs | extracellular vesicles | Microvesicles (mVs) extracted from MSC regulate inflammation, decreasing miR‐155 and pAkt levels | 2021 | [81] | |
Myocardial injury | intraperitoneal injections | bone marrow-derived MSCs | down-regulated TLR4 and NF -kB | The expression levels of TLR- 4, NF kappa B, and phosphorylated p38 decrease, pro-inflammatory cytokines and the phagocytic activity of macrophages decreases | 2016 | [83] |
intravenous injection | bone marrow-derived MSCs | MSCs improve cardiac function as indicated by a reduction in EF and FS and decrease the level of TNF-a, IL-1b, and IL-6 | 2011 | [84] | ||
intraperitoneal injections | bone marrow-derived MSCs | activation of mTORC2-Akt and inhibition of mTORC1-p70S6K signaling pathway | BMSCs activate the mTORC2-Akt signaling pathway and blocking the mTORC1-p70S6K signaling pathway | 2017 | [85] | |
Uveitis | foot pad injection | human uterine cervical stem cells | CM-hUCESC reduces pro-inflammatory cytokines and leukocytes in AqH and ocular tissues | 2016 | [102] |