Liver progenitor cell liver injury

Introduction

Liver progenitor cells (LPCs) play a crucial role in liver regeneration and repair, especially when the regenerative capacity of mature hepatocytes is compromised due to severe liver injury. These cells can differentiate into both hepatocytes and cholangiocytes, contributing to the restoration of liver function. However, their activation and proliferation are also associated with fibrosis, raising questions about their dual role in liver regeneration and injury.

Key Insights

Role in Regeneration and Fibrosis:
- LPCs are activated in response to liver injury and can differentiate into hepatocytes and cholangiocytes, aiding in liver regeneration when hepatocyte proliferation is impaired .
- The activation of LPCs is also linked to ductular reactions and progressive portal fibrosis, indicating a complex relationship between LPC activation and fibrogenesis .
Regulation of LPC Proliferation:
- TWEAK, a TNF family member, selectively stimulates LPC proliferation through its receptor Fn14, without affecting mature hepatocytes.
- Macrophages, particularly invading CX(3)CR1(high)CCR2(high) macrophages, play a significant role in LPC expansion by secreting pro-mitogenic cytokines like TNF-alpha.
Therapeutic Potential and Challenges:
- LPCs have shown potential in liver regeneration, with studies demonstrating their ability to repopulate liver parenchyma and regenerate hepatocytes and biliary epithelia in mouse models .
- Despite their regenerative capabilities, the heterogeneity of LPC populations and their association with fibrogenic responses pose challenges for their therapeutic use.
Microenvironment Influence:
- The hepatic microenvironment, including extracellular matrix components and various resident and recruited cells, significantly influences LPC activation and proliferation.
- Endothelial progenitor cells contribute to liver regeneration by promoting neovascularization and producing growth factors, enhancing the survival and proliferation of hepatocytes.

Conclusion

Liver progenitor cells are pivotal in liver regeneration, especially when the regenerative capacity of mature hepatocytes is compromised. They can differentiate into hepatocytes and cholangiocytes, aiding in tissue repair. However, their activation is also associated with fibrosis, indicating a dual role in liver injury and regeneration. The regulation of LPC proliferation involves various factors, including TWEAK and macrophages, and the hepatic microenvironment plays a crucial role in their activation. While LPCs hold therapeutic potential, their heterogeneity and fibrogenic responses present challenges that need to be addressed for effective clinical applications.

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Liver progenitor cell liver injury

Summary

Introduction

Key Insights

Conclusion

Sources and full results

Hepatic Progenitor Cells in Action: Liver Regeneration or Fibrosis?

Activated hepatic progenitor cells play a role in both liver regeneration and fibrosis during liver injury, with links to both regeneration and fibrosis.

TWEAK induces liver progenitor cell proliferation.

TWEAK selectively stimulates liver progenitor cell proliferation, potentially playing a role in human liver injury.

Invading macrophages play a major role in the liver progenitor cell response to chronic liver injury.

Invading macrophages play a crucial role in liver progenitor cell expansion during regeneration in chronic liver injury models, providing pro-mitogenic cytokines like TNFalpha.

Hepatic progenitor cells of biliary origin with liver repopulation capacity

Hepatic progenitor cells (HPCs) can contribute to liver regeneration and serve as a potential alternative to liver transplantation for liver disease.

Endothelial progenitor cell transplantation improves the survival following liver injury in mice.

Endothelial progenitor cell transplantation improves survival after liver injury in mice, promoting liver regeneration and potentially representing a new therapeutic strategy.

The progenitor cell dilemma: Cellular and functional heterogeneity in assistance or escalation of liver injury.

Liver progenitor cells play a crucial role in liver regeneration and tissue restitution, but their role and involvement in these processes are often controversial and may lead to increased fibrogenic response.

Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

The activation and expansion of hepatic progenitor cells in liver regeneration depend on the injury and the microenvironment, with potential therapeutic applications in various liver diseases.

Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice.

This study identified a bipotential liver progenitor cell in adult mice, with Sox9 expression as a key regulator, and identified potential regulators of liver progenitors.

Liver progenitor cells yield functional hepatocytes in response to chronic liver injury in mice.

Liver progenitor cells and biliary cells can differentiate into functional hepatocytes in response to chronic liver injury in mice.

Comparison of liver progenitor cells in human atypical ductular reactions with those seen in experimental models of liver injury

There are three types of liver progenitor cells in human atypical ductular reactions, and each type shows distinct biological and ultrastructural characteristics in experimental models of liver injury.

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