Abstract
The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role. Participation of blood-borne cells of the bone marrow origin in liver parenchyma regeneration has been proven but does not exceed 1-2% of newly formed hepatocytes. Liver regeneration is activated spontaneously after injury and can be further stimulated by cell therapy with hepatocytes, hematopoietic stem cells, or mesenchymal stem cells. Further studies aimed at improving the outcomes of cell therapy of liver diseases are underway. In case of liver failure, transplantation of engineered liver can become the best option in the foreseeable future. Engineering of a transplantable liver or its major part is an enormous challenge, but rapid progress in induced pluripotency, tissue engineering, and bioprinting research shows that it may be doable.
Highlights
Liver diseases pose a significant problem for national health care systems throughout the world [1,2,3,4]
Cell therapy and tissue/organ engineering are the main methods of regenerative medicine studied in the experimental setup and tested clinically
The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering should be delivered by the studies of cellular and molecular mechanisms of liver regeneration operating under physiological conditions, during enhanced functional loading, or after damage caused by disease, poisoning, or trauma [5]
Summary
Liver diseases pose a significant problem for national health care systems throughout the world [1,2,3,4]. Cell therapy (injection or transfusion of cell suspensions) and tissue/organ engineering are the main methods of regenerative medicine studied in the experimental setup and tested clinically. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering should be delivered by the studies of cellular and molecular mechanisms of liver regeneration operating under physiological conditions (homeostatic regeneration), during enhanced functional loading (adaptive regeneration), or after damage caused by disease, poisoning, or trauma (injury-induced regeneration) [5]. Research carried out with animal models showed that methods of regenerative medicine can provide beneficial effects surpassing those delivered by any other therapeutic approach excluding donor liver transplantation and that the mechanisms of those effects involve replacement of damaged cells or tissue and stimulation of the animal’s own regenerative potential. The scope of this paper is to review the mechanisms of liver regeneration and to describe current approaches aimed at enhancing liver regenerative capacities and at creating new engineered liver tissue and the whole engineered organ
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