Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Abstract

Mesenchymal stem/stromal cells (MSCs) are progenitors which share plastic-adherence capacity and cell surface markers but have different properties according to their cell and tissue sources and to culture conditions applied. Many recent publications suggest that MSCs can differentiate into hepatic-like cells, which can be a consequence of either a positive selection of rare in vivo pluripotent cells or of the original plasticity of some cells contributing to MSC cultures. A possible role of MSCs in hereditary transmission of obesity and/or diabetes as well as properties of MSCs regarding immunomodulation, cell fusion and exosome release capacities are discussed according to recent literature. Limitations in methods used to track MSCs in vivo especially in the context of liver cirrhosis are addressed as well as strategies explored to enhance their migratory, survival and proliferation properties, which are known to be relevant for their future clinical use. Current knowledge regarding mechanisms involved in liver cirrhosis amelioration mediated by naïve and genetically modified MSCs as well as the effects of applying preconditioning and combined strategies to improve their therapeutic effects are evaluated. Finally, first reports of GMP guidelines and biosafety issues in MSCs applications are discussed.

Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases

“…58 Similar results were obtained when MSC-conditioned media (MSC-CM) were applied instead, 58, 59 which suggests that MSCs might achieve a therapeutic effect in vivo via their secreted EVs, such as exosomes.…”

Ultrastructural Characteristics of Rat Hepatic Oval Cells and Their Intercellular Contacts in the Model of Biliary Fibrosis: New Insights into Experimental Liver Fibrogenesis

“…This particularly refers to cells deriving from epithelial-to-mesenchymal transition [12, 13, 19, 28, 33, 34], defined as the profibrogenic crosstalk between activated cholangiocytes that are related to HPCs and activated HSCs/myofibroblasts [13]. …”

Blood–brain barrier and foetal-onset hydrocephalus, with a view on potential novel treatments beyond managing CSF flow

“…In addition to unwelcome interactions of stem cells with the host immune system, there is evidence that they may promote tumorogenesis [123]. As animal models and first-in-man clinical studies have provided conflicting results, it is challenging to estimate the long-term risk for individual patients [124, 125]. Previous evidence has shown that the safety of stem cell therapies will depend on various factors including the differentiation status and proliferative capacity of the grafted cells, the timing and route of administration, and the long-term survival of the graft [126–130].…”