Studying on the importance exosomes pluripotent stem cell derived mesenchymal stromal cells (hipsc_MSCs) protect liver against hepatic ischemia
Studying on the importance exosomes pluripotent stem cell derived mesenchymal stromal cells (hipsc_MSCs) protect liver against hepatic ischemia
Niloofar torkzadeh,1,*Mozhgan shirazi,2
1. Department of Biochemistry, Islamic Azad University, Falavarjan, Iran 2. Department of Biology, Scince and Reserch Branch, Islamic Azad, university, tehran, iran
Introduction: in recent years, the MSCs derived from human induced pluripotent stem cells (hipscs) has been used in pre-clinical studies and showed better performance compared to the adult MSCs in terms of cell proliferation, immunomodulation, cytokines profiles production of microenvironment modulating exosomes and secretion of bioactive paracrine factors. It has been shown that hipsc_MSCs can prevent I/R damage in the kidney, liver and heart. Recent studies have further reported that EVs secreted by ADMSCs can deliver mirs such as mir181_5p and mir122 to inhibit the development of HF.
Methods: we reviewed about 22 articles are conducted from 2019 to 2023 in the world and Iran. We searched some key words such as exosome, mesenchymal stem cell, extracellular vesicles, mir150_5p, liver fibrosis in ScienceDirect, Elsevier, PubMed and SID.
we reviewed about 22 articles are conducted from 2019 to 2023 in the world and Iran. We searched some key words such as exosome, mesenchymal stem cell, extracellular vesicles, mir150_5p, liver fibrosis in ScienceDirect, Elsevier, PubMed and SID.
Results: the administration of MSCs as a therapy for liver disease holds great promise, it can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. Several studies have shown that exosome derived from MSCs play a major role in promoting hepatocyte proliferation and maintaining hepatocyte function. It was also confirmed that either circDIDOL over expression or mir 141_3p inhibition suppressed LX2 cells proliferation, resulted in cell cycle arrest and induced cell apoptosis. Moreover, mir141_3p inhibition reduced the protein levels of α-smooth muscle actin (α_SMA) and type Ι collagen (colΙ) inLX2 cells by elevating PTEN to suppress the AKT pathway. There is a study demonstrating that mir181_5p, which was secreted by ADMSCs can reduce liver fibrosis by reducing transforming growth factor beta (TGFβ) induced HSCs activation due to directly suppressing STAT3, Bcl2, Beclin, pathway and increasing autophagy. In addition, du et al, isolated EVs from ADMSCs and cocultured with HSCs, they found that ADMSCs derived EVs containing mir150_5p attenuate hepatic fibrosis by inhibiting cxcl1 expression. Cxcl1 is ligand for cxc chemokine receptor2, which has also been documented to be expressed in HSCs. Further experimental results indicated that circCDK3 mediated liver fibrosis by regulating the mir17_5p, KAT2b axis, and KAT2B can promoted MFGE8 transcription by H3 acetylation. Hence HbMSCs derived exo circCDK13 can inhibit liver fibrosis. More over recent studies have demonstrated that hbMSCs_EXs inhibited HSCs activation via the wnt/βcatenin pathway in vitro and in vivo. MSCs express antigen cluster of differentiation CD105, CD73 and CD90 but they lack CD45, CD34 and human leukocyte antigen HLA class Π. In a culture system that allowed MSCs to be in contact directly with HSCs the suppressed HSC proliferation by upregulating the notch1 expression and down regulating the p13k, AKT pathway, a critical pathway inducing HSC proliferation in HSCs, although the exact mechanism by which notch1 decreased p_AKT in HSCs has not been elucidated. It has also been reported that MSCs prevented HSCs from entering this phase by upregulating the inhibitors of cell proliferation such as p27kip, and p21cip1, and downregulating the accelerators of cell cycle namely, cyclinD and PERK. Phosphorylated ERK1/2 that is highly associated with HSC proliferation was also found to be reduced in HSCs cocultured with MSCs.
Conclusion: To summarize, the current study revealed that EVs derived from ADMSCs deliver mir150_5p to down regulated the expression of CXCL1, which inhibits the development of HF. Exosome could intracellularly activated the generation of sip and sk1 activity in the target hepatocytes. The results indicated that hbMSCs_EXs are responsible to induce the recovery of markers associated with improved liver function, inhibition of inflammation and increased hepatocyte regeneration.