Stratified medicine in a dish using human induced pluripotent stem cells

Last week at the World Stem Cells & Regenerative Medicine Congress, Ludovic Vallier, Senior Non-Clinical MRC Fellow at University of Cambridge hIPS cells.

Ludovic’s group uses Yamanaka-method IPS cells as a platform for the production of a range of specialist tissues. The key idea is that such cells may be valuable tools for the testing of medicinal products for specific patient groups. In short, that the cells may be used in the development of stratified medicines.

Ludovic’s team is working to derive human IPS cells in high throughput conditions. It has demonstrated how derivation is becoming increasingly efficient.  Working with the Sanger Institute, the group has sought to ensure that genomic integrity is maintained. A panel of 20 IPS cell lines, deriving from patients with different ages, sex and indications, has been created.

The type of cell types that can be generated, are impressive:  pancreas, ventral foregut into lung cells,- in each case characterised by key markers.  Similarly, having derived “gut spheroids” from hind gut endoderm, such spheroids may be further matured.  And, of course, hepatocyte-like cells from human IPS cells.  The functional characteristics of these human IPS cell derived liver cells have close functional equivalence to natural occurring hepatocytes.  However, significantly, it is clear that there is significant variability between different lines.  Most of these differences appear to be of genetic, as opposed to sex, age/epigenetic, origin.  Plainly, this is a significant insight for those with an interest in the development of stratified medicines, opening up the real prospect of valuable research tools,- for example, using a well plate approach to predictive toxicology.

It was very apparent that large scale hIPSC derivation is highly feasible, with a wide diversity of endoderm cells being generated in vitro. Importantly, artificial DE derivatives appear similar to their natural counterparts, a feature which suggests promise in the realm of regenerative medicine as well as drug testing.  Ludovic Vallier, Marcus Yeo and Roger Pedersen have recently founded a Cambridge spin-out company, Definigen to exploit these technologies.

Check back here in a couple of days for the full presentation.

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