Induced pluripotent stem cells could soon be used in Japanese human trials

28 February 2013
Researchers from RIKEN Center for Developmental Biology in Kobe have submitted an application to the Japanese health ministry for permission to start recruiting patients with macular degeneration for an iPS cell-based trial. 

Prof Martin Pera comments on the significance of this development and warns that researchers and regulators need to ensure that preclinical evidence for safety and efficacy is strong and participants are aware of risks:

For many years, Masayo Takahashi has carried out leading research on the differentiation of pluripotent stem cells into the neural and retinal lineages. She and her colleagues at the RIKEN Center for Developmental Biology are amongst the pioneers in this field. With this experience, they are well placed to undertake translational studies.

Age-related macular degeneration is in many ways a favorable disease target for the first human trials of iPS cells. Clinical studies with embryonic stem cell derived therapeutics for macular degeneration are underway or scheduled to begin soon in a number of centers worldwide. This experience will help to guide the design and conduct of trials of IPS cells, and will provide invaluable early stage comparisons of the two modalities from  the standpoint of efficacy and safety. Only small numbers of cells are required to treat a patient with macular degeneration, thus limiting the risk of tumor induction by low levels of contaminating cells.  Also, modern imaging technology allows us to trace the fate of the grafted cells noninvasively and at high resolution. In the unfortunate event that the injected cells were to give rise to lesions that might endanger a patient, the grafts are easily accessible for surgical removal.

Despite these considerations, there are still concerns over the genetic and epigenetic stability of induced pluripotent stem cells, and their ability to differentiate efficiently into cells of therapeutic potential. Whilst many of these concerns apply equally to embryonic stem cells, individualization of patient therapy with iPS cells poses additional challenges for cell production and safety assessment. It will be very important for the future of the field that this trial meet these challenges. Current technology for safety assessment of any cell therapy, based on ES or iPS cells, has real limitations.

As with the first trial of human ES cells, the details of the teams' plans for cell production and safety assessment are not (to my knowledge) in the public domain, so in a sense the entire field is very dependant on this group and the Japanese regulatory agencies to ensure that their preclinical evidence for safety and efficacy is very strong. It is also most important that the public realize that this is experimental medicine that carries unknown risks. There is an added burden on this investigators to explain this in the clearest possible terms.

Prof Pera's comments feature in today's Nature article - Stem cells cruise to the clinic.