Takahashi team IPS cell vision paper marks major stem cell milestone

Ring the bell for a stem cell milestone.

There’s been a whole lot of commotion about the NEJM article yesterday documenting the experiences of three women with macular degeneration who were blinded by non-FDA approved stem cell eye injections of fat stem cells at a business in Florida, but in the same issue of the journal there also was some encouraging stem cell news that came in the form of essentially a mirror image of the bad news paper. We can call it the “stem cell good news-bad news” issue of NEJM.

Takahashi IPS transplant

Mandai, et al. NEJM 2017 Figure 1C

The good news was the publication of the first paper on clinical use of IPS cell-derivatives in a human patient. A big milestone. This groundbreaking manuscript comes from the pioneering team in Japan led by stem cell scholar Dr. Masayo Takahashi. I’ve written extensively in the past about the work of Takahashi and her team with IPS cells, and she received my Stem Cell Person of the Year Award back in 2014.

In the new paper they detail their data from the clinical study using sheets of retinal pigmented epithelial cells (RPEs) made from IPS cells in this case derived from the patient herself for autologous use. Remarkably in Figure 1C (above) you can see the actual transplanted RPE sheet in the eye of the patient (see dark area indicated by white arrow). The most encouraging part of this study was that the patient’s vision remained stable (rather than declining as expected) following the treatment. Was that due to the transplant? We can’t be sure.

Also, this is just a beginning as it is just one patient, but it is very exciting and represents a big milestone for the IPS cell and broader stem cell field, providing real hope for patients with vision loss along with parallel ESC-based clinical trial work as well.

This paper contrasts so much with the report from the other one in the same issue on the terrible outcomes from the stem cell clinic’s use of fat stem cells in the eye. While the use of fat stem cells themselves is highly questionable in my view for this application, the biggest differences between the two approaches is that the Takahashi team work was extremely rigorous, careful, based on extensive preclinical studies, had governmental approval, and was in essence science-based clinical medicine.

For instance, the Takahashi team was appropriately cautious with Patient 2 since the cells exhibited some genomic changes. At least in part for that reason, moving forward this clinical work will primarily focus on allogeneic use of IPS cells via an IPS cell bank being developed by Shinya Yamanaka.

We can also look to other future IPS cell-based trials coming on-line including for Parkinson’s Disease and other conditions, which are likely to be allogeneic as well in Japan, but probably autologous here in the U.S.

I love a good stem cell milestone!

Stem Cell Person of the Year 2014: Masayo Takahashi (高橋 政代)

Masayo Takahashi

Dr. Masayo Takahashi,  Asahi photo

Congratulations to Masayo Takahashi (高橋 政代), MD, PhD, the winner of the 2014 Stem Cell Person of the Year Award.

Dr. Takahashi received this award including the $2,000 prize for her exceptional achievements in stem cell research in 2014. She was selected as the winner from a stellar group of top 12 finalists this year.

Takahashi leads a team doing high-risk, high reward research that is conducting the first induced pluripotent stem cell (IPSC) clinical study in humans ever. I interviewed Takahashi at the beginning of this year and you can learn more about her research and vision for the future from reading that interviewMonkey stem cell RPEs

The Takahashi team clinical study is intended to examine the safety of a human retinal pigmented epithelial cell (RPE) product made from each patients’ own IPSCs. You can see at right RPEs produced by her team from monkey pluripotent stem cells.

In an astonishing feat of speedy clinical translation, Takahashi’s team transplanted its first macular degeneration patient recently on September 12, only 7 years after human IPSCs were first ever published. The usual timeline for such translation would be 20 years. In that regard, in a recent interview I did with him, Nobel Laureate Shinya Yamanaka had this to say of Takahashi and her work:

I was surprised that after the announcement of human iPSCs in 2007, Dr. Takahashi told me that she would bring iPSC to the bedside within five years. I thought it possible technically speaking, but doubted it could be done so soon, since we needed to improve the technology and get government approval. It took 7 years, which is remarkable considering the work required. Both the accomplishment and the speed at which it was achieved are testaments to Dr. Takahashi’s leadership and her strong team.

Her achievements extend beyond this year to an outstanding long-term track record in vision research including a very impressive track record of highly-cited publications. Takahashi is physician scientist, who is a faculty member and Project Leader at the Laboratory of Retinal Regeneration at the CDB at RIKEN. Some of her nominators for the Stem Cell Person of the Year Award described her as a “transformative” and “courageous” stem cell scientist. Below you can see a TEDx talk from just a few months ago by Takahashi explaining her work.

Takahashi joins previous Stem Cell Person of the Year Award recipients Roman Reed and Elena Cattaneo as outside-the-box thinkers who to take risks to make outstanding new developments in the arena of stem cell research with the goal of helping others.

More about the Stem Cell Person of the Year Award. I fund this prize myself as a way of giving back to the stem cell community and recognizing transformative people who take risks to help others. It is to my knowledge the only annual, international science-related prize personally funded by a professor.

Putting the IP in iPS cells: patent war looming?


By Paul Knoepfler

Will intellectual property (IP) wars over patent rights to one of the most exciting new stem cell technologies hold back getting novel therapies to patients?

Unfortunately, it’s very possible.

Induced pluripotent stem (iPS) cells are very cool stem cells made from non-stem cells through a process called cellular reprogramming.

iPS  cells have essentially all of the same properties and powers as embryonic stem (ES) cells, but without the potential ethical complexity of utlizing a human blastocyst for their generation.

Pretty amazing, huh?

iPS cells have huge therapeutic potential both directly via potential cell therapies (e.g. for treatment of macular degeneration) and indirectly as the basis for disease modeling and drug screens.

All of this sounds wonderful and it is, but of course you know there had to be a catch, right?

The huge potential problem here is the issue of intellectual property (IP) rights to iPS cells.

All the talk and the slew of publications about potentially using iPS cells to develop therapies to help patients is exciting in theory, but unfortunately the reality is that it is not entirely clear if most researchers are, from a legal standpoint, even allowed to develop and commercialize iPS cell-based therapies at all.

The patent landscape for iPS cells is complicated to put it mildly. A Google patent search for “induced pluripotent stem cells” produced almost 200,000 results.

A search for “cellular reprogramming produced more than 1,000 results.

I’m not sure all of these results are really separate patents, but still….that’s a big complicated mess.

To me simplistically it seems like Yamanaka and his institution should own the rights, but clearly it’s not so simple.

Can any Dr. Joe Shmoe clearly without IP rights to iPS cells develop a therapy?

So if, for example, my lab wanted to develop an iPS cell-based therapy to treat an important disease, would it be possible to do so?

I don’t know. It sure seems risky to me to develop a therapy based on a technology that someone else owns even if I’m not entirely sure who that someone else is.

What about other companies or researchers? Many are working feverishly to develop iPS cell-based therapies, but to my knowledge almost none of them have any IP rights to iPS cells.

It seems like a recipe for trouble to me if not an outright nightmare.

And also I wonder could some other companies be challenging (directly or indirectly by their actions) the Japanese IP and patents on iPS cells?

For example, the company Advanced Cell Technology (ACT; stock symbol ACTC) is most well-known perhaps for its ES cell-based therapies in clinical trials for macular degeneration, but it has clearly indicated that  it is developing an iPS cell-based platelet product and perhaps other iPS cell-related products.

But does ACTC in fact have the necessary IP rights to do this? Will they have to pay someone else for the right to use iPS cell technology? ACT has indicated that they have some IP rights to iPS cell-like technology, but what exactly does that mean? Will they be sued if they try to commercialize an iPS cell-based product?

I’ve heard that Stanford is also working on an iPS cell-based therapy with every intent to make it into a stem cell-based treatment to be used for patients….but does Stanford have the legal right to do that?

I’m not aware of Stanford have any IP claim to iPS cell technology at all. Have they signed a licensing agreement with another institution that has a patent for iPS cells?

What about all the other universities and researchers working on clinical translation of iPS cells?

It is no exaggeration to say there are likely dozens of institutions around the world wanting to commercialize iPS cell-based products.

Will they all have to pay expensive licensing fees or end up in court?

…or will the patent holders voluntarily and freely allow others to commercialize iPS cell-based medical treatments?

I don’t think so.

This could get really messy.

Meet the Retina Institute of Japan: translating iPS cells to the clinic

Retina Institute of JapanThe stem cell field is still abuzz about induced pluripotent stem (iPS) cells 7 years after their discovery.

This amazing embryonic stem cell-like cells can be made with no embryo and have the potential for truly patient specific therapies as well as dish-in-a-dish modeling and drug discovery.

How will iPS cells get to patients?

A big player is the Japanese company Institution, Riken.

iPS cells are being commercialized and at the forefront far seems to be the Retina Institute of Japan (RIJ), which appears to be just one (but a leading) commercial arm of Riken’s efforts to translate iPS cells to the bedside and generate income. The image above is from the RIJ homepage and appears to be a human iPS cell colony. Their goal is to use iPS cell-produced retinal pigmented epithelial cells (RPE) to treat macular degeneration.

Still most stem cell researchers do not know about RIJ.

I looked them up and started with their mission statement, getting a translation from my friend Noriko. I think the mission statement is very cool:

On 2/24/2011, we established a company Retinal Japan Institute, with the goal of next generation medicine and drug and instrument development.

” Delivering happiness to the people in the world by bringing iPS cells into clinic” – this is a huge responsibility.
However, we are not afraid of this huge responsibility.
The road to the goal will be full of difficulties.
No footprints, maps, nor signs
There is no fast track to achieve this goal, and it may take 10 or 20 years.
However, no one can stop us starting the first step toward the goal today.
No one can stop us assembling a team and make efforts toward the goal.
We will start with a small dot, the dots will form a line, then a line will form a large road.
This large road will be filled with joy of patients who benefit from the iPS treatments.
You do not need to hesitate.
Let’s start.
One reason that I like this motto so much is that it is passionate, but also realistic and extolls patience.
I am hopeful, despite earlier concerns that I have expressed, that RIJ will indeed take the time it needs to do the thorough animal safety testing studies that are crucial before making the big jump into studies in humans.
One issue is of course that it has competition. For example, Advanced Cell Technology (ACT; ACTC) has an extremely similar product made from embryonic stem cells that is already well into combined phase I/II FDA-approved clinical trials. However, in the end patient safety has to come first or everybody loses in my opinion.