05 September 2019

Cornea from iPSK

The Japanese were the first to transplant a human cornea from reprogrammed stem cells

Svetlana Yastrebova, N+1

For the first time in the world, Osaka University staff performed a human corneal transplant, the basis of which was the descendants of induced pluripotent stem cells (iPSCs), and not the biomaterial of deceased donors, the journal Nature reports. This was told by the main author of the work, Koji Nishida (Kohji Nishida), at a press conference in Osaka University on August 29. One of the main advantages of such a transplant is the absence of immune system cells in it and, as a result, a low probability of rejection.

The cornea is a transparent part of one of the membranes of the eyeball, it serves to refract light and is formed from epithelial cells. Unfortunately, quite often this part of the eye is injured or the biochemical processes in the corneal epithelium are disrupted so that it reduces its transparency. Vision deteriorates at the same time, and the deterioration often progresses.

The way out is to change the cornea to a donor one. Usually transplants are taken from dead people. New corneas take root well, but there is still a risk that the recipient's body will reject them, since along with the cornea, some more cells of someone else's immune system are inevitably transplanted. In addition, there is a shortage of donor material: about 1,600 people are currently waiting for transplantation in Japan.

Ophthalmologists from Osaka University has proposed a way to increase the number of corneal transplants available using induced pluripotent stem cells. These are non-stem cells, most often fibroblasts, which underwent epigenetic reprogramming (that is, the activity of their genes was changed) and thanks to it returned to an undifferentiated state, having lost their specialization. Cells of various types can be obtained from iPSCs, the final result depends on which mixture of differentiation factors acted on them.

The corneal epithelium, which was obtained from the donor's IPSC, does not contain cells of the immune system of this donor, which means that the probability of rejection of such a transplant is lower. Experiments on rabbits have shown that this procedure improves vision and does not cause a strong immune response. In this case, the animals were transplanted corneas from human iPSCs, that is, the donor was even of a different kind.

The first recipient of the cornea, whose epithelium grew from the descendants of induced pluripotent stem cells, was a Japanese citizen aged about 40 years. She suffered from reticular corneal epithelial dysgenesis. Simply put, his cells were not being updated properly and therefore could not provide sufficient corneal transparency.

On July 25, 2019, a thin layer of corneal tissue obtained from the donor's IPSC was transplanted into the patient's left eye. On August 23, she was discharged from the hospital. It is reported that the woman's eyesight has improved since the operation.

Kyoji Nishida expects that the transplant will work properly until the end of the patient's life, but, of course, in the coming year her well-being will be closely monitored. "We have just started working with the first patient and are at a stage where we need to monitor [the condition of the recipients] very carefully," he said. At the same time, the authors of the study suggest that in a few years, corneal transplantation from IPSC descendants will become widespread.

Nishida received permission to use IPSC to create corneal transplants in March 2019. Then the Ministry of Health, Labor and Welfare of Japan conditionally approved corneal transplantation operations from the descendants of induced pluripotent stem cells to four volunteers who suffer from degeneration of this eye shell. Also this year, the Japanese government approved creation of chimeric human and animal embryos.

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