Management of Liver Failure: From Transplantation to Cell-Based Therapy

Abstract

The severe shortage of deceased donor organs has driven a search for alternative methods of treating liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion. Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks. This review summarizes the current literature on the physiological role of endogenous stem cells in liver regeneration and on the therapeutic benefits of exogenous stem cell administration with specific emphasis on the potential clinical uses of mesenchymal stem cells. Moreover, critical points that still need clarification, such as the exact identity of the stem-like cell population exerting the beneficial effects, as well as the limitations of stem cell-based therapies, are discussed.

3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo

“…Therefore, scalable tissue models and regenerative therapies are urgently sought. While cell transplantation or bioartificial liver devices offer promise to treat failing liver function, the shortage of good primary human hepatocytes has seriously restricted both endeavours (Demetriou et al 2004 ; Francipane et al 2011 ; Thompson et al 2015 ; Dhawan 2015 ; Forbes et al 2015 ; Oldhafer et al 2016 ). Therefore, the establishment of renewable PSC systems has generated much excitement in the field.…”

Generation of Hepatobiliary Cell Lineages from Human Induced Pluripotent Stem Cells: Applications in Disease Modeling and Drug Screening

“…A plethora of studies has established that MSCs can differentiate in vitro into multiple lineages, although satisfactory results were obtained only in the case of MSC conversion into mesodermal lineages (osteocytes, chondrocytes, and adipocytes) [ 33 ]. Yet, MSCs remain a promising source for liver repair thanks to their well-documented paracrine activities [ 34 , 35 ]. More recently, the development of the induced pluripotent stem cell (iPSC) technology, which allows to convert one cell type into another [ 36 ], has created a potentially inexhaustible supply of cells for large-scale toxicity testing and drug screening, and an outstanding source of patient-specific cells for disease modeling.…”