Exosomes Derived from Adipose Mesenchymal Stem Cells Promote Regeneration of Injured Liver in Minipigs.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Mesenchymal Stem Cells*/metabolism ; Mesenchymal Stem Cells*/cytology ; Swine, Miniature* ; Exosomes*/metabolism ; Exosomes*/transplantation ; Liver Regeneration* ; Adipose Tissue*/cytology ; Adipose Tissue*/metabolism ; Liver*/metabolism ; Liver*/pathology; Animals ; Swine ; Cell Proliferation ; Reperfusion Injury/therapy ; Reperfusion Injury/metabolism ; Hepatectomy ; Cytokines/metabolism ; Male

Hepatic ischemia/reperfusion injury (IRI) is an important factor affecting liver regeneration and functional recovery postoperatively. Many studies have suggested that mesenchymal stem cells (MSCs) contribute to hepatic tissue repair and functional recovery through paracrine mechanisms mediated by exosomes. Minipigs exhibit much more similar characteristics of the liver to those of humans than rodents. This study aimed to explore whether exosomes from adipose-derived MSCs (ADSCs-exo) could actively promote liver regeneration after hepatectomy combined with HIRI in minipigs and the role they play in the cell proliferation process. This study also compared the effects and differences in the role of ADSCs and ADSCs-exo in the inflammatory response and liver regeneration. The results showed that ADSCs-exo suppressed histopathological changes and reduced inflammatory infiltration in the liver; significantly decreased levels of ALT, TBIL, HA, and the pro-inflammatory cytokines TNF-α, IL-6, and CRP; increased levels of the anti-inflammatory cytokine IL-10 and the pro-regeneration factors Ki67, PCNA, CyclinD1, HGF, STAT3, VEGF, ANG1, ANG2; and decreased levels of the anti-regeneration factors SOCS3 and TGF-β. These indicators above showed similar changes with the ADSCs intervention group. Indicating that ADSCs-exo can exert the same role as ADSCs in regulating inflammatory responses and promoting liver regeneration. Our findings provide experimental evidence for the possibility that ADSCs-exo could be considered a safe and effective cell-free therapy to promote regeneration of injured livers.

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31972757 National Natural Science Foundation of China

Keywords: exosomes; hepatectomy; ischemia reperfusion; liver regeneration; mesenchymal stem cells; minipig

0 (Cytokines)

Date Created: 20240627 Date Completed: 20240627 Latest Revision: 20240629

20240629

PMC11203699

10.3390/ijms25126604

38928308