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

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.

Effects of age on biological and functional characterization of adipose-derived stem cells from patients with end-stage liver disease

“…A crucial factor that may influence clinical outcomes of cell therapy/transplantation procedures, as well as the success of tissue engineering, is the proliferative, migratory, antiapoptotic and differentiation capacities of the cells used (27). The ability to expand cells without losing function is key to successfully culturing ADSCs for therapeutic purposes.…”

Interleukin‐35 in immune‐related diseases: protection or destruction

“…Hepatitis virus causes destruction of liver parenchymal cells, leading to severe liver disorders, such as cirrhosis and hepatocellular carcinoma . Hepatitis is a common and frequently occurring disease in the clinic, its incidence being highest in Asia . The T‐cell‐mediated immune response plays an important role in the pathogenesis of the disease .…”

“…75 Hepatitis is a common and frequently occurring disease in the clinic, its incidence being highest in Asia. 76 The T-cell-mediated immune response plays an important role in the pathogenesis of the disease. 77 Studies suggest that unstimulated human Treg cells do not express IL-35; 8 however, substantial up-regulation of EBI3 and P35, not IL-10 and transforming growth factor-b, was observed in activated human Treg cells compared with conventional T cells.…”

Self‐Renewal Capability of Hepatocytic Parental Progenitor Cells Derived From Adult Rat Liver Is Maintained Long Term When Cultured on Laminin 111 in Serum‐Free Medium

“…cell transplantation, engineered hepatocellular tissue constructs, and bio-artificial liver devices, have been considered as alternatives to whole-liver transplantation. (1)(2)(3) A large number of healthy hepatocytes are required for these therapies to compensate for their insufficient hepatic function. However, it is quite difficult to routinely obtain healthy human hepatocytes because of severe liver donor shortages and a lack of methods to expand functional hepatocytes.…”