Our stem cell technologies

ReNeuron's approach to stem cell therapy

Stem cells can be derived from human tissues at any stage of development, from the early embryo to the adult.

Early human embryonic stem cells (or 'hES' cells) are capable of forming cells from any tissues. However, the cells are likely to form tumours when transplanted.

As the tissues develop through the fetal and adult stages, the resident stem cell populations have a progressively diminished developmental potential and lose their inherent tumour- forming capacity, becoming somatic stem cells, also known as lineage- or tissue-restricted stem cells. Somatic stem cells are therefore likely to be the safest type for use in cell therapy treatments.

ReNeuron has built its technology platform around human somatic stem cells derived from the fetus, which we believe offer the most viable route to the clinic for stem cell therapy. The principal factors supporting this somatic stem cell approach can be characterised as follows:

Multipotency: somatic stem cells are able to differentiate into the specific cell types found in the organ from which they originated, removing the need for the cell manipulation or sorting when using hES cells
Quality: somatic stem cells from the fetus are free from adventitious virus contamination
Safety: somatic stem cells can be controlled more readily than hES cells once implanted, removing the possible risk of tumours

The power of ReNeuron's platform stem cell technology is that it can be applied to any somatic stem cell, whether the starting material is derived from the embryo, fetus or adult.

The development of ReNeuron's stem cell lines

ReNeuron was founded on the basis of original studies in the 1990s using mouse stem cell lines developed by Dr John Sinden (a founder of the Company) and his colleagues at the Institute of Psychiatry, Kings College London. Some 20 peer-reviewed papers over the past seven years have described how one of these original stem cell lines was able to restore cognitive and motor function in a range of animal disease models. These included stroke, dementia, ageing and traumatic brain injury, where the damaged area was re-constituted with normal functioning brain cells.

The challenge for ReNeuron was to transfer this early success with mouse stem cells to their human equivalent. A major breakthrough occurred in 2002 when the Company identified the platform technology needed to successfully and cost-effectively grow selected human stem cells into banks of cell lines capable of treating thousands of patients. This technology, utilising the c-myc gene, also enables the production of stable cells which retain their essential characteristics. ReNeuron has the exclusive worldwide licence to this technology and has developed a controllable variant of it, c-mycER^TAM. The diagram below outlines ReNeuron's approach to stem cell line production using its c-mycER^TAM technology.

Although ReNeuron's competitors have managed to grow and bank stem cells, we are not aware that any of these cells have been shown to be stable in character (i.e. that they demonstrate genotypic and phenotypic stability). This is a crucial factor and one that may determine whether regulatory authorities give approval to treat patients.

ReNeuron's c-mycER^TAM technology allows for the efficient creation of hundreds of stem cell lines from an individual tissue sample. ReNeuron has developed a unique screening platform that enables optimal stem cell lines for each indication to be progressed into pre-clinical development. The cells are tested for cell characteristics, growth and bankability, as well as their capacity to engraft, with minimal immune rejection by the host, in the relevant disease model.

Schematic illustrating ReNeuron's approach to stem cell therapy

(click to view full size image)

The ideal characteristics of a stem cell line

We believe that the ideal characteristics of a stem cell line that can be taken forward into clinical development are:

Multipotent somatic cells that can develop into specific tissues
Cells that are derived from a single founder cell (clonal cells)
Genetically stable cells with normal chromosomes
Cells that have the ability to differentiate into appropriate cell types, in vitro and in vivo
Cells that can be grown in large numbers and stored
Cells that are safe
Cells whose migration, once implanted, is limited to areas of tissue damage
Cells that are efficacious in recognised animal models
Cells whose provenance is fully documented

This combination of characteristics provides cell lines that have the greatest potential to be stable and safe to use. These are the primary criteria set by regulatory authorities in order for a cell therapy to be acceptable. Cells with properties that diminish attainment of these standards are more likely to raise concerns with regulators. ReNeuron's stem cell strategy ensures closest compliance to these requirements and it is this that we believe gives the Company a strong and unique competitive lead in the field.

The advantages of ReNeuron's stem cell lnes

The major advantages of ReNeuron's approach over other approaches to the generation of viable somatic stem cell lines are:

The ability to generate a large number of genetically stable, clonal stem cell lines efficiently from a single fetal tissue sample
From this, the ability to generate 'banks' of clinical grade cell lines, sufficient to treat thousands of patients
The ability of these stem cells to differentiate into large numbers of mature somatic cells showing normal functional features
The ability of the cells to be frozen and thawed with maximum viability, providing the basis for a dosage form for use in a clinical setting

Alternative approaches for growing bankable stem cell cultures are being developed elsewhere. However, as mentioned above, we believe that the cell lines generated are likely to be unstable in terms of their biological properties and will also differ each time cell lines are derived. These alternative approaches are therefore likely to encounter considerable regulatory, practical, ethical and commercial hurdles in their development.

Proof of principle using ReNeuron's stem cell lines

ReNeuron has tested a number of its lead neural stem cell lines in a series of validated pre-clinical efficacy models of stroke and other central nervous system diseases. The results of a number of these studies have been published and presented at key conferences.

Presentations and Abstracts

The non-therapeutic potential of ReNeuron's stem cell lines

Stem cells have significant potential beyond their use in cell therapy treatments for disease. They can, for instance, be used in the drug discovery process as a screening tool against which drug candidates can be screened for toxicity. ReNeuron has generated important data, demonstrating that certain of its stem cell lines exhibit the unique characteristics necessary for them to perform a key role in these non-therapeutic applications. We believe that the use of ReNeuron's cell lines in these areas will provide certain key advantages over the cell types currently used.

ReNeuron has developed a range of cell lines – its ReNcell^TM range – to commercialise the potential of these non-therapeutic applications.

ReNcell^TM Programmes page

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