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Updated: Jun 22, 2025
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Published on: May 3, 2024
Exosomes Derived from Adipose Mesenchymal Stem Cells Promote Regeneration of Injured Liver in Minipigs
Yue Wang1, Chenxi Piao1, Tao Liu1
1College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Abstract:
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.
Insights
Exosomes from adipose-derived mesenchymal stem cells (ADSCs-exo) promote liver regeneration and reduce inflammation after injury in minipigs. These cell-free exosomes offer a potential therapy for injured livers, mirroring the effects of the stem cells themselves.
Area of Science:
- Regenerative Medicine
- Hepatology
- Cell Biology
Background:
- Hepatic ischemia/reperfusion injury (HIRI) impairs liver regeneration and postoperative recovery.
- Mesenchymal stem cells (MSCs) and their exosomes are implicated in hepatic tissue repair via paracrine signaling.
- Minipigs serve as a relevant preclinical model due to liver similarities with humans.
Purpose of the Study:
- To investigate if adipose-derived MSC exosomes (ADSCs-exo) promote liver regeneration after hepatectomy with HIRI in minipigs.
- To elucidate the role of ADSCs-exo in cell proliferation during liver regeneration.
- To compare the therapeutic effects of ADSCs and ADSCs-exo on inflammatory response and liver regeneration.
Main Methods:
- Administration of ADSCs-exo to minipigs undergoing hepatectomy and HIRI.
- Assessment of histopathological liver changes and inflammatory cell infiltration.
- Quantification of liver injury markers (ALT, TBIL, HA), cytokines (TNF-α, IL-6, IL-10, CRP), and regeneration factors (Ki67, PCNA, VEGF, etc.).
Main Results:
- ADSCs-exo significantly reduced liver histopathology and inflammatory infiltration.
- Key liver injury markers and pro-inflammatory cytokines decreased, while anti-inflammatory cytokine IL-10 increased.
- ADSCs-exo promoted pro-regeneration factors and suppressed anti-regeneration factors, mirroring ADSC treatment effects.
Conclusions:
- ADSCs-exo effectively regulate inflammatory responses and promote liver regeneration in a minipig model of HIRI.
- ADSCs-exo demonstrate comparable therapeutic potential to ADSCs, suggesting a viable cell-free therapeutic strategy.
- ADSCs-exo represent a promising, safe, and effective cell-free therapy for promoting regeneration in injured livers.
