World-first Transplant to Treat Macular Degeneration Could Augur Rise of iPS Cell Banks
On March 28, a Japanese man in his 60s became the first person to receive cells derived from induced pluripotent stem (iPS) cells that had been donated by another person.
The surgery is expected to set the path for more applications of iPS cell technology, which offers the versatility of embryonic stem cells without the latter’s ethical taint. Banks of iPS cells from diverse donors could make stem cell transplants more convenient to perform, while slashing costs.
iPS cells are created by removing mature cells from an individual (from their skin, for example), reprogramming these cells back to an embryonic state, and then coaxing them to become a cell type useful for treating a disease.
In the recent procedure, performed on a man from Hyogo prefecture, skin cells from an anonymous donor were reprogrammed and then turned into a type of retinal cell that was transplanted onto the retina of the patient who suffers from age-related macular degeneration. Doctors hope the cells will stop progression of the disease, which can lead to blindness.
In a procedure performed in September 2014 at the Kobe City Medical Center General Hospital, a Japanese woman received retinal cells derived from iPS cells. They were taken from her own skin, though, and then reprogrammed. Such cells prepared for a second patient were found to contain genetic abnormalities and never implanted.
The team decided to redesign the study based on new regulations, and no other participants were recruited to the clinical study. In February 2017, the team reported that the one patient had fared well. The introduced cells remained intact and vision had not declined as would usually be expected with macular degeneration.
In today’s procedure — performed at the same hospital and by the same surgeon Yasuo Kurimoto — doctors used iPS cells that had been taken from a donor’s skin cells, reprogrammed and banked. Japan’s health ministry approved the study, which plans to enroll 5 patients, on 1 February.
Using a donor’s iPS cells does not offer an exact genetic match, raising the prospect of immune rejection. But Shinya Yamanaka, the Nobel Prize-winning stem-cell scientist who pioneered iPS cells, has contended that banked cells should be a close enough match for most applications.
Yamanaka is establishing an iPS cell bank, which depends on matching donors to recipients via three genes that code for human leukocyte antigens (HLAs) — proteins on the cell surface that are involved in triggering immune reactions. His iPS Cell Stock for Regenerative Medicine currently has cell lines from just one donor. But by March 2018, they hope to create 5-10 HLA-characterized iPS cell lines, which should match 30%-50% of Japan’s population.
Use of these ready-made cells has advantages for offering stem cell transplants across an entire population, says Masayo Takahashi, an ophthalmologist at the RIKEN Center for Developmental Biology who devised the iPS cell protocol deployed in today’s transplant. The cells are available immediately — versus several months’ wait for a patient’s own cells — and are much cheaper. Cells from patients, who tend to be elderly, might have also accumulated genetic defects that could increase the risk of the procedure.
At a press conference after the procedure, Takahashi said the surgery had gone well but that success could not be declared without monitoring the fate of the introduced cells. She plans to make no further announcements about patient progress until all five procedures are finished. “We are at the beginning,” she says.
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