Exploiting in silico modelling to enhance translation of liver cell therapies from bench to bedside

Candice Ashmore-Harris, Evangelia Antonopoulou, Simon M. Finney, Melissa R. Vieira, Matthew G. Hennessy, Andreas Muench, Wei-Yu Lu, Victoria L. Gadd, Alicia J. El Haj, Stuart J. Forbes, Sarah L. Waters

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Cell therapies are emerging as promising treatments for a range of liver diseases but translational bottlenecks still remain including: securing and assessing the
safe and effective delivery of cells to the disease site; ensuring successful cell engraftment and function; and preventing immunogenic responses. Here we highlight three therapies, each utilising a different cell type, at different stages in their clinical translation journey: transplantation of multipotent mesenchymal stromal/signalling cells, hepatocytes and macrophages. To overcome bottlenecks impeding clinical progression, we advocate for wider use of mechanistic in silico modelling approaches. We discuss how in silico approaches, alongside complementary experimental approaches, can enhance our understanding of the mechanisms underlying successful cell delivery and engraftment. Furthermore, such combined theoretical-experimental approaches can be exploited to develop novel therapies, address safety and efficacy challenges, bridge the gap between in vitro and in vivo model systems, and compensate for the inherent differences between animal model systems and humans. We also highlight how in silico model development can result in fewer and more targeted in vivo experiments, thereby reducing preclinical costs and experimental animal numbers and potentially accelerating translation to the clinic. The development of biologically-accurate in silico models that capture the mechanisms underpinning the behaviour of these complex systems must be reinforced by quantitative methods to assess cell survival post-transplant, and we argue that non-invasive in vivo imaging strategies should be routinely integrated into transplant studies.
Original languageEnglish
Article number19
Number of pages10
Journalnpj Regenerative Medicine
Volume9
DOIs
Publication statusPublished - 9 May 2024

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