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Human placenta mesenchymal stem cell-derived exosomes delay H 2 O 2 -induced aging in mouse cholangioids.
- Source :
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Stem cell research & therapy [Stem Cell Res Ther] 2021 Mar 22; Vol. 12 (1), pp. 201. Date of Electronic Publication: 2021 Mar 22. - Publication Year :
- 2021
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Abstract
- Background: Cholangiocyte senescence is an important pathological process in diseases such as primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Stem cell/induced pluripotent stem cell-derived exosomes have shown anti-senescence effects in various diseases. We applied novel organoid culture technology to establish and characterize cholangiocyte organoids (cholangioids) with oxidative stress-induced senescence and then investigated whether human placenta mesenchymal stem cell (hPMSC)-derived exosomes exerted a protective effect in senescent cholangioids.<br />Methods: We identified the growth characteristics of cholangioids by light microscopy and confocal microscopy. Exosomes were introduced concurrently with H <subscript>2</subscript> O <subscript>2</subscript> into the cholangioids. Using immunohistochemistry and immunofluorescence staining analyses, we assessed the expression patterns of the senescence markers p16 <superscript>INK4a</superscript> , p21 <superscript>WAF1/Cip1</superscript> , and senescence-associated β-galactosidase (SA-β-gal) and then characterized the mRNA and protein expression levels of chemokines and senescence-associated secretory phenotype (SASP) components.<br />Results: Well-established cholangioids expressed cholangiocyte-specific markers. Oxidative stress-induced senescence enhanced the expression of the senescence-associated proteins p16 <superscript>INK4a</superscript> , p21 <superscript>WAF1/Cip1</superscript> , and SA-β-gal in senescent cholangioids compared with the control group. Treatment with hPMSC-derived exosomes delayed the cholangioid aging progress and reduced the levels of SASP components (i.e., interleukin-6 and chemokine CC ligand 2).<br />Conclusions: Senescent organoids are a potential novel model for better understanding senescence progression in cholangiocytes. hPMSC-derived exosomes exert protective effects against senescent cholangioids under oxidative stress-induced injury by delaying aging and reducing SASP components, which might have therapeutic potential for PSC or PBC.
Details
- Language :
- English
- ISSN :
- 1757-6512
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Stem cell research & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 33752720
- Full Text :
- https://doi.org/10.1186/s13287-021-02271-3