Good stem cell news as Takahashi IPS Cell Trial to Resume

Masayo TakahashiSome good news today as the pioneering induced pluripotent stem (IPS) cell trial led by Dr. Masayo Takahashi will resume.

This clinical study with a focus on macular degeneration has been on hold for quite some time due to regulatory changes in Japan. There had also been concerns over mutations in the 2nd patient’s IPS cell product.

As previous signs had indicated, the new clinical work will have an allogeneic focus, most likely drawing IPS cells from a bank.

According to a Japan Times article:

For the second trial, the CDB will develop retinal tissues from iPS cells supplied by Kyoto University’s Center for iPS Cell Research and Application, headed by Nobel laureate Shinya Yamanaka, the creator of the pluripotent cells.

Transplants of CDB-developed retinal tissues will be conducted at Kobe City Medical Center General Hospital and Osaka University Hospital.

This is exciting and I’m very curious to see how this clinical work develops.

In 2014, Dr. Takahashi won my Stem Cell Person of the Year Award.

This may also signal a door opening for other IPS cell trials in Japan including one for Parkinson’s Disease by Jun Takahashi.

Landmark IPSC clinical study on hold due to genomic issue

IPSC RPE sheetThe pioneering induced pluripotent stem cell (IPSC) clinical study in Japan led by top stem cell clinical researcher Dr. Masayo Takahashi has been stopped reports the WSJ in Japan. This development is confirmed by other sources and in a PDF report by RIKEN (in Japanese here).

One patient was transplanted in September 2014 with their own IPSC-derived retinal pigment epithelial cells (using an innovative RPE sheet, see image) for treatment of macular degeneration.

The study then moved on to a possible second patient, whose IPSC did not pass a genomic validation step. Reportedly, these IPSC contained a mutation, potentially in a known oncogene, which is a serious concern. Thus, the team decided to at least temporarily suspend the trial pending a possible redesign. The new plan could involve a change in how the IPSC are produced. For example, the team is reportedly considering the possible use of allogeneic IPSC as well, which could come from CiRA (Center for iPS cell Research and Application, Kyoto University).

It remains unclear at this time whether the mutation in the second patient’s IPSC was pre-existing in the patient’s skin cells or if it occurred during the reprogramming process itself. This is a critically important question to resolve. If the mutation was caused by/associated with reprograming then that would be a deeper issue.

Overall, this situation is of course a concern, but it also reflects the very rigorous and appropriate degree of caution that this team was using in validation studies. Notably, the first transplanted patient is apparently doing well.

I hope to learn more details from Dr. Takahashi and will pass that along on the blog when possible. She has also been tweeting about this development (you can follow her at @masayomasayo). Until we learn more it is advisable to take a cautious approach in interpreting this development.