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Published on: June 29, 2021
Contribution of dermal-derived mesenchymal cells during liver repair in two different experimental models
Li Tan1, Tingyu Dai1, Dengqun Liu1
1Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing 400038, China.
Abstract:
Progressive liver disease is a major health issue for which no effective treatment is available, leading to cirrhosis and orthotopic liver transplantation. However, the lack of availability of donor organs and other adverse factors including rejection limit its extensive clinical application. Cell-based therapy using mesenchymal stem/stromal cells (MSCs) may represent an attractive therapeutic option. Dermal-derived mesenchymal cells (DMCs) are attractive as one of the abundant sources from which to isolate mesenchymal cells for therapeutic applications and can be easily accessed with minimal harm to the donor. In this study, we used two different animal models to investigate potential therapeutic effect of DMCs transplantation in liver injury. We found that DMCs administration alleviated liver fibrosis and restored the liver function in fibrotic mice induced by CCl4. Furthermore, in an acute irradiation induced damage model, a unique population of DMCs could engraft into the liver tissue for a long period, exhibiting the phenotype of both mesenchymal cells and macrophage cells, and improve the survival of mice exposed to 8 Gy lethally total-body irradiation. These discoveries provide important evidence that DMCs therapy has a beneficial effect on liver injury, and provide new insight into liver injury therapy depending on the alternative cells.
Insights
Dermal-derived mesenchymal cells (DMCs) show promise for treating liver injury. This cell therapy alleviated liver fibrosis and improved liver function in animal models, offering a potential new treatment for progressive liver disease.
Area of Science:
- Regenerative Medicine
- Hepatology
- Stem Cell Biology
Background:
- Progressive liver disease is a significant global health concern with limited effective treatments, often necessitating liver transplantation.
- Current limitations in liver transplantation include organ scarcity and post-transplant complications like rejection.
- Cell-based therapies, particularly using mesenchymal stem/stromal cells (MSCs), present a promising alternative for liver regeneration.
Purpose of the Study:
- To investigate the therapeutic potential of dermal-derived mesenchymal cells (DMCs) in preclinical models of liver injury.
- To evaluate the efficacy of DMC transplantation in mitigating liver fibrosis and restoring liver function.
- To assess the engraftment and functional characteristics of DMCs in an acute radiation-induced liver damage model.
Main Methods:
- Two distinct animal models were employed: carbon tetrachloride (CCl4)-induced liver fibrosis and acute irradiation-induced liver damage.
- Dermal-derived mesenchymal cells (DMCs) were administered to assess their therapeutic effects.
- Engraftment, phenotypic analysis, and survival rates were evaluated in the irradiation model.
Main Results:
- DMC administration significantly alleviated liver fibrosis and restored liver function in CCl4-treated fibrotic mice.
- In the irradiation model, a unique DMC population successfully engrafted into liver tissue long-term.
- These engrafted DMCs exhibited a dual mesenchymal and macrophage phenotype, enhancing survival in lethally irradiated mice.
Conclusions:
- Dermal-derived mesenchymal cells (DMCs) demonstrate significant therapeutic benefits for liver injury, including fibrosis and radiation damage.
- DMCs possess unique properties, such as long-term engraftment and a dual phenotype, contributing to their regenerative capacity.
- DMC therapy represents a novel and potentially effective strategy for managing progressive liver disease and improving outcomes in critical liver injury.
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