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Cell-based therapies of liver diseases: age-related challenges

Authors Yarygin KN, Lupatov AY, Kholodenko IV

Received 9 October 2015

Accepted for publication 20 October 2015

Published 1 December 2015 Volume 2015:10 Pages 1909—1924

DOI https://doi.org/10.2147/CIA.S97926

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Supriya Swarnkar

Peer reviewer comments 2

Editor who approved publication: Dr Richard Walker

Konstantin N Yarygin, Alexei Y Lupatov, Irina V Kholodenko

Laboratory of Cell Biology, Institute of Biomedical Chemistry, Moscow, Russia

Abstract: The scope of this review is to revise recent advances of the cell-based therapies of liver diseases with an emphasis on cell donor’s and patient’s age. Regenerative medicine with cell-based technologies as its integral part is focused on the structural and functional restoration of tissues impaired by sickness or aging. Unlike drug-based medicine directed primarily at alleviation of symptoms, regenerative medicine offers a more holistic approach to disease and senescence management aimed to achieve restoration of homeostasis. Hepatocyte transplantation and organ engineering are very probable forthcoming options of liver disease treatment in people of different ages and vigorous research and technological innovations in this area are in progress. Accordingly, availability of sufficient amounts of functional human hepatocytes is crucial. Direct isolation of autologous hepatocytes from liver biopsy is problematic due to related discomfort and difficulties with further expansion of cells, particularly those derived from aging people. Allogeneic primary human hepatocytes meeting quality standards are also in short supply. Alternatively, autologous hepatocytes can be produced by reprogramming of differentiated cells through the stage of induced pluripotent stem cells. In addition, fibroblasts and mesenchymal stromal cells can be directly induced to undergo advanced stage hepatogenic differentiation. Reprogramming of cells derived from elderly people is accompanied by the reversal of age-associated changes at the cellular level manifesting itself by telomere elongation and the U-turn of DNA methylation. Cell reprogramming can provide high quality rejuvenated hepatocytes for cell therapy and liver tissue engineering. Further technological advancements and establishment of national and global registries of induced pluripotent stem cell lines homozygous for HLA haplotypes can allow industry-style production of livers for immunosuppression-free transplantation.

Keywords: cell aging, rejuvenation, liver engineering, liver cell therapy

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