September 11, 2013

expert reaction to new research into induced pluripotent stem (iPS) cells

A Nature paper demonstrated it is possible to reprogramme adult cells into pluripotent stem cells within living mice.

Prof. Chris Mason, Professor of Regenerative Medicine, University College London, said:

“Undoubtedly being able to reprogram cells in the body to different cell types will be useful in producing future therapies capable of transforming patients’ lives. However, the cells that will be useful will not be the pluripotent stem cells (iPS cells), but their more specialized (‘adult’) offspring. Thus this paper is an interesting proof of concept of the first step in the process (in vivo adult cells to iPS cells), but it still needs these iPS cells to be safely converted to useful ‘adult’ cell types in the body. The major challenge will be tightly controlling every step in this potential approach to treating patients in order to deliver clinical benefits whilst avoiding significant complications.”

Dr Ilaria Bellantuono, Reader in Stem Cell and Skeletal Ageing, MRC/Arthritis Research-UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), University of Sheffield, said:

“Reprogramming in vitro has allowed any cell of the body to be turned into pluripotent stem cells, meaning they can produce any cell in the body, in the petri dish in the laboratory. What this paper shows for the first time is that this can now be achieved directly in vivo in mice.

“This paper is very exciting. Clearly nobody wishes to do this for therapeutic purposes because this leads to the formation of tumours called teratomas. However this is a proof of concept that pluripotency can be achieved in vivo. This opens up opportunities to investigate ways to partially reprogram cells in the body to a desired state of dedifferentiation. In principle, these partially dedifferentiated cells could then be induced to differentiate to the cell type of choice inducing regeneration in vivo without the need of transplantation.”

Prof Robin Lovell-Badge, Head of Developmental Genetics, MRC National Institute for Medical Research, said:

“The fact that it is possible to get reprogramming in vivo to give iPS cells is quite predictable and I think most labs would not have tried this because it was likely to be detrimental to the animals, with little scientific gain. The paper does highlight one useful piece of knowledge of relevance to safety – we need to be careful how we handle the reprogramming factors, especially if they are contained within viral vectors, otherwise people exposed to them are very likely to develop teratomas, which are not going to be very good for the person.

“Nevertheless, they did find something that could be scientifically very interesting, namely that the in vivo iPS cells (or at least some of them) appear to correspond to a very early embryonic stage – more akin to cells of the morula than the inner cell mass of the blastocyst. But at this stage the data is simply phenomenological – i.e. I want to know why? Why should reprogramming in vivo give a different outcome to reprogramming in vitro? It suggests that the latter is missing something – perhaps something complex like an immune system that selects for cells characteristic of an earlier embryonic stage, or something simple, like the levels of oxygen, which is generally lower in vivo than in standard tissue culture conditions.

“However, as it is, I can’t see this being useful with respect to making human iPS cells – I would not volunteer to have the factors expressed within me. Although one interesting possibility would be to begin with a mouse containing human cells or tissues, and to use this as the in vivo system to obtain the human iPS cells.”

‘Reprogramming in vivo produces teratomas and iPS cells with totipotency features’ by Serrano et al., published in Nature on Wednesday 11 September.