Japan stem cell clinical studies rapidly piling up

Shibata, et al. Cell reports 2018, corneal structures made from hIPSCs
Shibata, et al. Cell reports 2018, corneal structures made from hIPSCs
Shibata, et al. Cell reports 2018, corneal structures made from hIPSCs
Shibata, et al. Cell reports 2018, corneal structures made from hIPSCs

Japan is a leader in stem cell and regenerative medicine research, and in particular in clinical translation toward the bedside. Induced pluripotent stem cell (IPSC)-based investigational therapies are rightly an area of focus in Japan given their invention by Nobel Laureate Shinya Yamanaka. Small clinical studies based on IPSC have been initiated there for several diseases including related to vision loss and Parkinson’s Disease.

David Cyranoski over at Nature reports on a new, different stem cell clinical effort in Japan for vision loss with “Japan poised to allow ‘reprogrammed’ stem-cell therapy for damaged corneas.” Readers are probably much more familiar with the efforts of Masayo Takahashi‘s team working with IPSC-based retinal pigmented epithelial cell therapy being studied for macular degeneration. The Takahashi work is focused on the retina in the back of the eye, whereas the new work led by Kohji Nishida is studying stem cells for the cornea at the front of the eye (see some of their data at left from a 2018 Cell Reports study on making corneal sheet-like structures from human IPSCs). Note that in this figure the term ICEC means “hiPSC-derived corneal epithelial cells.”

I expect authorities to give the go-ahead for this new clinical study.

Another new article points to an additional area of novel work. See the piece Ministry OKs 1st iPS cell therapy trial for spinal cord injuries in The Asahi Shimbun. The team leaders are Hideyuki Okano and Masaya Nakamura. The study will begin with low doses (2 million cells) to assess safety.

Over at The Scientist, there’s also this opinion piece Ethical Challenges in Using iPS Cells to Treat Paralysis on the new trial raising questions as well. In the piece, Professors John Loike and Martin Grumet raise what I think are some legitimate concerns about the new IPSC-based spinal cord injury trial. They argue this hasn’t been enough transparency about this study and also they note that in preclinical work some cells exhibited abnormal proliferation.

This is the 2nd stem cell therapy study for spinal cord injuries recently in Japan. The other one, where an approach was actually approved for marketing to patients, spurred a lot of debate because there wasn’t much published data to support it and the premise based on infusion of MSCs seemed puzzling.

Overall, Japan is taking more regulatory gambles on innovative stem cell-based therapies. It’s a high-risk, high-reward approach. I’m very curious to see where things will stand there in five years. Here in the U.S. the newish Regenerative Medicine Advanced Therapy (RMAT) designation program is also trying to speed along stem cell clinical trial work, but doesn’t involve actually approving still-investigational products for marketing to patients.

5 Comments


    • Teratogenicity means toxic effects on a fetus, which is not a relevant issue with iPSCs. I think you mean that undifferentiated iPSCs can form teratomas when transplanted to immunodeficient mice. This is not an issue, either, because no one is transplanting undifferentiated iPSCs. All of the studies use iPSCs to generate specific cell types- corneal epithelium, retinal pigment cells, dopamine neurons, cardiac muscle- taking advantage of the iPSC’s ability to differentiate into a lot of different cell types…their pluripotency


  1. I wonder if, for marrow transplant recipients with graft versus host disease, iPSC’s can be derived from the recipient’s donor blood cells to generate tissue grafts for GVHD-affected areas such as, well, corneas.


    • Are you suggesting that tissues attacked by graft versus host disease could be replaced with tissues that match the graft? Interesting idea. I wouldn’t mind having a discussion about whether this makes sense.


  2. There is a paper (https://www.nature.com/articles/bmt2010247) that demonstrated successful treatment of severe dermal GVHD using a skin graft from the original donor (sister). But I think using tissue is impractical for recipients with unrelated donors. If one is a hematopoietic stem cell recipient, then being a chimera, it seems one has a natural store of potential iPSC’s to draw on.

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