Safety of stem cells supported by mouse study

Tissue derived from induced pluripotent stem cells (iPS cells) causes 'limited or no immune response' in mice, a study published in Nature has found. Additionally, it reports no difference in the immune response to tissue derived from iPS cells and embryonic stem cells (ES) cells.

The findings come after a study in 2011, led by Professor Yang Xu, claimed that iPS cells - but not ES cells - could face rejection by the immune system (reported in BioNews 608).

Dr Masumi Abe, lead author of the new study, criticised the approach taken by Professor Xu in which iPS cells and ES cells were directly transplanted into genetically identical mice without having first been differentiated into more specific cells.

Dr Abe also criticised their assessment of the immune reaction elicited by the iPS cells. Direct transplantation of the iPS cells resulted in the formation of teratomas - non-malignant tumours made up of cells from all three embryonic germ layers. This was used to indicate the pluripotency of the iPS cells, but Dr Abe claims this could also have caused the cells to be attacked and destroyed by the immune system of the mice. Dr Abe writes: 'Given that teratomas are a type of tumour, it is not surprising that they elicit immunological reactions in transplant patients'.

Instead, Dr Abe and his team at the National Institute of Radiological Sciences in Japan, first transformed iPS cells into other cell types such as skin and bone marrow tissue before these were transplanted into mice. Dr Abe thinks it is more important to assess the effects of these differentiated cells.

To generate terminally differentiated tissue Dr Abe mixed iPS cells or ES cells into early mouse embryos to make chimaeric embryos. After the embryos grew into adult mice they used the tissue derived from the stem cells in their transplantation experiments. The transplants derived from iPS cells and ES cells were equally successful and induced 'negligible' immune responses.

Although these results are promising, this study has also been subject to criticism. Professor Xu considers the approach of transplanting tissue from chimaeric mice to be 'flawed'. He explains that the limited immune response observed could be because the most immunogenic cells were rejected as the mice developed.

Indeed, Dr Abe himself acknowledges it is now necessary to confirm that the tissue created from iPS cells in vitro is not rejected.

Dr Jakub Tolar from the University of Minnesota, USA remarked: 'It's helpful that they've done this, but it is absolutely different when you go to something that is cultured'.

Professor Konrad Hochedlinger, a stem-cell scientist at Massachusetts General Hospital, USA, told Nature News the result will most likely 'calm people down' about iPS cells. 'It is definitely reassuring' he added.

'Based on what we know at this time from mice, iPS cells are as good as ES cells, and should be as safe', Professor Hochedlinger said.