4.7 Review

Liver cell therapies: cellular sources and grafting strategies

Journal

FRONTIERS OF MEDICINE
Volume 17, Issue 3, Pages 432-457

Publisher

SPRINGER
DOI: 10.1007/s11684-023-1002-1

Keywords

liver regeneration; hepatocytes; cholangiocytes; stem cells; organoids; regulatory mechanisms; transplantation; grafting strategies

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The liver is composed of various types of cells and has a high regenerative capacity. The main cell types, hepatocytes and cholangiocytes, work together with non-parenchymal cells to perform liver functions. The regulation of liver cells involves complex interactions between the extracellular matrix and soluble signals. Recent advancements in genetic sequencing have allowed for a better understanding of liver cell composition and regulation. Furthermore, breakthroughs in cell transplantation strategies offer potential solutions for treating end-stage liver diseases.
The liver has a complex cellular composition and a remarkable regenerative capacity. The primary cell types in the liver are two parenchymal cell populations, hepatocytes and cholangiocytes, that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells, endothelia and various hemopoietic cell populations. The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates, the extracellular matrix, working synergistically with soluble paracrine and systemic signals. In recent years, with the rapid development of genetic sequencing technologies, research on the liver's cellular composition and its regulatory mechanisms during various conditions has been extensively explored. Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases, offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation. This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair. Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.

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