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Development of conditionally immortalised cell lines as novel cell models of disease and for cell transplantation

12 December 2014

UCL research developed reagents that enabled cells to be grown indefinitely in vitro and differentiated when growth conditions were altered. Two companies were established to exploit this research, ReNeuron (now worth £63.5m and publicly traded on the London AIM market) and XCellSyz.

Professor Parmjit Jat (UCL Institute of Neurology) established the critically important concept of conditional immortalisation, whereby cells can be grown indefinitely but undergo a rapid cessation of growth and differentiate (become more specialised) when growth conditions are altered. This enabled him to develop "Immortomouse", a novel strain of mice that can be used to derive conditionally immortal cells from a wide variety of tissues. This was patented by the Ludwig Institute for Cancer Research (LICR) and the Medical Research Council (MRC), with Professor Jat as one of the inventors, and has been sold worldwide by Charles River Laboratories. Many research groups and companies worldwide have subsequently used this approach to develop conditionally immortal cell lines that can undergo differentiation.

Lonza overcomes [the limitations of immortalized cell lines] using a temperature dependent, conditional immortalization approach utilizing Large T-Antigen that allows the immortalization to be reversed and the cells to revert to their original characteristics. This allows development of cell lines from a wide range of human and animal tissues, and of novel models relevant to drug discovery based on lines from people with particular diseases. - Lonza AG 

Collaborative work between Professor Jat, Dr John Sinden (now Chief Scientific Officer of ReNeuron) and Professor Jeffrey Gray led to the development of cells that can be maintained indefinitely and exhibit multipotent properties (the potential to differentiate into multiple but limited cell types) in vitro and in vivo. This raised the possibility of successfully developing multipotent clonal cell lines that can be used in human graft neurosurgery, with the capacity to migrate to areas of central nervous system damage, and restore specific neurological and cognitive deficits. This was the basis for the establishment of ReNeuron in 1997, with the primary objective of developing novel human cell lines for transplantation. The initial focus was to develop stem cell lines for generating new neurons and brain cells to reverse damage to brain tissue caused by stroke. ReNeuron was valued at £63.5m in 2013 and is publically traded on the London AIM market. ReNeuron has used its cell expansion and screening technologies to develop stem cell therapies for conditions such as stroke where there are few alternative treatments. Unlike conventional drug treatments that treat symptoms, stem cell treatments treat the underlying cause of the disease. The aim is to develop cells that can be readily administered 'off-the-shelf' to any eligible patient without the need for additional drug treatments.

ReNeuron has developed stem cell therapy for the treatment of patients left disabled by stroke and is also developing stem cell therapies for other conditions such as critical limb ischaemia, a serious and common side effect of diabetes, and blindness-causing diseases of the retina. The company has also developed a range of stem cell lines for non-therapeutic applications for use in academic and commercial research.

XCellSyz was established in 2005 as a spin-out from UCL by Professor Peter Shepherd (then of the UCL Department of Biochemistry and Molecular Biology); Professor Jat was on the Scientific Advisory Board. XCellSyz was bought by Cambrex and then Lonza AG, the current owners. Professor Jat, with research support from ReNeuron, developed reagents for conditional immortalisation of human cells. These counteract the changes to cells caused by the process of immortalisation - meaning cells revert back to their original characteristics and are truer to cells found in intact tissue. Lonza now supplies these reagents as well as conditionally immortal cells to the worldwide scientific community.