October 1, 2020

The Niche

Knoepfler lab stem cell blog

Japan conditionally approves new IPS cell-based heart study

Where do things stand with IPS cell translational research?

The newest development is that regulators in Japan just have given conditional approval to an Osaka University team to an induced pluripotent stem (IPS) cell-based study for ischemic heart disease.

Screenshot of Yoshiki Sawa slide on IPS cell approach for heart disease
Screenshot of Yoshiki Sawa slide on IPS cell approach for heart failure, which is similar to approach for ischemic heart disease.

For years IPS cell-based products have been on-again off-again in active clinical study for macular degeneration, work led by Dr. Masayo Takahashi. The new heart disease study is led by Yoshiki Sawa. This appears to be the third conditionally approved IPS cell study in Japan. I’m not clear on whether both other studies included in the total of 3 here are from Dr. Takahashi or not.

Here is information on the study design:

“The approved plan will cover patients with ischemic cardiomyopathy, or hearts weakened by narrowed or blocked arteries preventing blood from reaching parts of the heart muscle. Three people aged between 18 and 79 will have two round cell sheets made from the iPS cells of other people attached to the surface of their hearts. The sheets will each be 0.05 millimeters thick and several centimeters in diameter. Researchers will examine the safety of the procedure, checking for cancer, immunorejection and other such signs, and will also observe changes in the function of the patients’ hearts.”

It has a number of key differences with the previous conditionally approved studies beyond the organ of focus. Perhaps the most striking aspect of the new study is that it will use far more cells:

“This is the third case of clinical research involving transplants using iPS cells to be approved. In the previous two cases, groups including the Riken research institute are transplanting several hundred thousand cells in the treatment of intractable diseases. The number of cells in the latest research is far greater — at around 100 million. As there is a risk of iPS cells turning cancerous, it will be crucial for researchers to guarantee the safety of the process.”

Ideally, we don’t want any undifferentiated IPS cells in the transplanted product, but that’s a tall task with 100 million cells. Past studies have suggested that not all IPS cells have tumorigenic potential including in a transplantation context so a few amounts 100 million overall may not cause problems. This will have to be carefully monitored as stressed in the  Mainichi piece. From a second Mainichi article we have a quote on this issue from Dr. Sawa:

“Even if a tumor does develop, because the cells come from another person, it is expected that it will disappear after the suppressants are withdrawn and the person’s natural immune system kicks in.”

I hope he’s right about that.

This is exciting investigational work, but high-risk in my view. It will be interesting to follow.

You can learn more from a slide set from Dr. Sawa’s research here (and see image above from one such slide).

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