July 6, 2020

The Niche

Knoepfler lab stem cell blog

Landmark: patient receives first ever iPS cell based transplant

IPS cell pioneer Masayo Takahashi
IPS cell clinical pioneer Masayo Takahashi.

In a major first for the stem cell and regenerative medicine fields, a patient in Japan today received a pioneering transplant of a retinal pigmented epithelial (RPE) sheet made from induced pluripotent stem (iPS) cells, also known by the acronym IPSC.

This is the first ever iPS cell-based transplant into a human.

The patient is reported to be a 70-something Japanese woman suffering from macular degeneration and the procedure was performed by Dr. Yasuo Kurimoto and other specialists. I highly recommend the article by David Cyranoski, one of my favorite science writers, linked to in the previous sentence for more on the transplant.

The patient is clearly a brave hero. The team transplanted a huge (from a bioengineering perspective) 1.3 x 3.0 mm sheet of RPEs into the retina of the patient, who did not have any clear immediate side effects from the procedure. Keep in mind again that this sheet was made indirectly from the patients own skin cells so it is an autologous (or self) transplant, a notion that 10 years ago would have seemed entirely like sci-fi.

This is not only a huge milestone, but also an astonishingly fast translation of iPS cell technology from the bench to the bedside. Talk about warp speed science.

Nobel laureate Shinya Yamanaka first reported the creation of mouse and human iPS cells just eight and seven years ago, respectively. To get to the clinic so soon thereafter is one of the fastest biomedical translational pathways in history.

How was this possible?

In part this is a story of an extraordinary level of commitment to iPS cell technology by Japan and its scientists including the team led by the amazing Dr. Masayo Takahashi (pictured above) and of course Yamanaka too.

The work was also made possible by Yoshiki Sasai, who did pioneering work in retinal differentiation from pluripotent stem cells. So we are talking about fantastic scientists dedicated to translation and a government willing to fund them generously to make this a reality.

Another important element to this story is that Japan has a clinical translation pipeline that is now faster with recent changes in regulations than that of the US. For example, this and future iPS cell-based transplants were approved as part of a clinical study, a type of clinical research mechanism that doesn’t exist in the US. It is safe to say that the same technology with the same research team and outstanding level of funding would still be at least a few years away from their first patient in the US due to the different regulatory scheme. Another indication of the unusual speed here was indicated in the Cyranoski piece:

Kurimoto performed the procedure a mere four days after a health-ministry committee gave Takahashi clearance for the human trials (see ‘Next-generation stem cells cleared for human trial‘).

With this difference between regulatory frameworks not only comes the potential for speedier clinical innovations, but also the uncertain potential for risks from first in-human studies.

In a sense we have an experiment inside of an experiment here.

We have the actual clinical studies as an experiment and then we have the larger context of a regulatory experiment too. Nobody knows how it will turn out. One can certainly have hope from the fact that the Takahashi team’s preclinical studies were reportedly encouraging from a safety perspective, although that data has not yet been published. Also, on the positive side we have the encouraging results from the ongoing clinical trials from Advanced Cell Technology (ACT) using a similar approach to macular degeneration, but employing human embryonic stem cells to make the RPEs.

For the vision impaired and the broader stem cell field, it is heartening to have two such capable teams working to cure blindness with pluripotent stem cells.

Admittedly, we are now in uncharted territory, which is both exciting and a bit unsettling too. That’s the reality with cutting edge biomedical science and going after huge goals like curing blindness. What an exciting time to be in the stem cell field.

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