Dr Hassan Rashidi

Senior Research Associate in Stem Cell & Regenerative Medicine

(UCL) Hassan completed his PhD on extra-mesodermal differentiation potential of human mesenchymal stem cells and graduated from the University of Nottingham in 2012. Following this, he worked as a postdoctoral research fellow in Prof. Kevin Shakesheff’s laboratory to develop novel methodologies to heal large bone defects. In October 2014, He joined Prof. David Hay's laboratory at the University of Edinburgh to develop an extracorporeal liver device. Hassan has developed a novel fully-defined and GMP-ready protocol to efficiently generate pluripotent stem cell-derived 3D hepatospheres, which remains metabolically active for over a year in culture.

Development of a novel xeno-free protocol to generate phenotypically stable three dimensional hepatospheres from human pluripotent stem cells

Abstract: Liver disease is the fifth most common cause of death in the UK and the death toll is rising. Liver transplantation is an effective procedure to treat end stage liver disease and organ failure, however donor organ shortage represents a significant problem. Therefore, there is a clear imperative to develop novel and scalable alternatives to transplant to treat human liver disease. The use of the major metabolic cell type of the liver, the hepatocyte, as a cell based therapy to treat human metabolic liver disease has proved successful [1]. However, like the whole organ itself, primary human hepatocytes are a limited resource with which to tackle the worldwide issue of liver disease. The pluripotent stem cells can provide a credible alternative with which to generate a stable source of quality assured human liver tissue for the clinic. To this end, several protocols have been developed to efficiently generate hepatocyte-like cells (HLCs), mainly employing two-dimensional differentiation systems [2-8]. Despite recent improvements [9-11], 2D-derived HLCs exhibit foetal features and unstable phenotype in vitro, limiting their clinical application. However, current differentiation procedures deliver tissue lacking appropriate function and stability. Efforts to overcome these limiting factors have led to the building of three dimensional (3D) cellular aggregates [12]. However, they are not suitable for clinical application due to their reliance on animal-derived and undefined biological components [13-17]. Our studies focused on the development of 3D liver tissue under xeno-free and GMP-ready conditions. Notably, generated 3D tissues exhibited stable liver phenotype for over 1 year in culture and provided critical liver support in three separate animal models, including immunocompetent recipients. We believe that our study delivers a blue-print to effectively treat certain liver diseases in the future.