Japan university tackles aging with transplanted pluripotent stem cells

Yamanaka factors-derived IPS cells demonstrate success in human clinical trial.

A research team from Osaka University in Japan has concluded that a clinical trial of transplanted IPS cell-derived corneal tissue was safe and effective – further evidence that cellular reprogramming with Yamanaka factors is moving towards scalable therapies.

Longevity.Technology: The clinical trial spanned several years and used corneal tissues derived from induced pluripotent stem cells. The tissue was transplanted into four almost-blind patients, and, according to the research team, none of the patients experienced rejection or tumorigenicity of the transplanted cells and all saw improvements in their symptoms, with three experiencing improved eyesight, with one improving from 0.15 to 0.7. Importantly, all were free of side effects one year later.

IPS cells can be generated from any adult cell, with Yamanaka factors – a group of protein transcription factors from four master genes. These induced stem cells demonstrate the significant quality of pluripotency – they can differentiate into all other cell types of the body. This is incredibly useful both for research and for therapy.

The cornea is a transparent membrane approximately 11 mm in diameter and 0.5 mm thick; it is the eye’s outermost protective layer and serves as both a lens to focus vision and a barrier against foreign substances.

Corneas can weaken, get thinner and change shape over time and degenerative conditions, such as endothelial dystrophy, cause the cornea to deteriorate with age.

The team hope that this progress will result in a new treatment will solve issues such as transplant rejection and a chronic shortage of corneal donors. With an estimated 12.7 million people worldwide waiting for a corneal transplantation, this treatment is desperately needed.

The transplants were performed between July 2019 to December 2020 on four patients in their 30s to 70s who were all suffering from corneal epithelial stem cell deficiency; this is a condition caused by loss of the cells in the eye that produce the cornea and leads to deteriorating eyesight and associated loss of vision. There is no effective treatment other than a transplant.

The procedure for the clinical trials involved culturing corneal cells from another individual’s iPS cells stored at Kyoto University to create 0.05-millimetre thick sheets of corneal tissue. These tissue sheets were then transplanted into the patients.

After monitoring the patients for a year, the team confirmed that the transplanted tissues were not rejected and that corneal clouding had improved.

The next step will be a clinical trial in 2023, with the aim of putting the treatment into practical use in the next three to four years.

“This could be a revolutionary treatment that could overcome the challenges that existing treatment has faced, such as a shortage of cornea donors or transplant rejection,” said Koji Nishida, a professor of ophthalmology at Osaka University [1].

“We hope this procedure will come to be performed around the world,” he added [2].

IPS cells had additional success recently – in a recent article published in Biomaterials, a team led by researchers at Osaka University and Kyoto University demonstrated that using cartilage tissue derived from human stem cells could help prevent the loss of functionality from intervertebral disc degeneration [3], which can lead to serious conditions such as spinal deformity. 

[1] https://www.cbsnews.com/news/japan-stem-cells-transplanted-worlds-oldest-population/
[2] https://english.kyodonews.net/news/2022/04/c8af6b7913b2-japan-team-proves-ips-based-cornea-transplant-safe-in-world-1st-trial.html
[3] https://www.sciencedirect.com/science/article/pii/S0142961222001302