Induced pluripotent stem cells (iPSCs) are adult cells that are reprogrammed back to an embryonic state. They hold huge promise as regenerative medicines. Researchers at the NIH’s National Eye Institute (NEI) have developed such a therapy to prevent blindness in dry age-related macular degeneration (AMD), and they have produced positive animal data that set the stage for a human trial.

AMD is characterised by the loss of the retinal pigment epithelium (RPE), a thin cell layer which nurtures photoreceptors, the light-sensing cells in the retina. The new therapy is designed to replace dying RPE cells and therefore protect the eye before vision loss occurs.

The NEI scientists took blood cells from AMD patients, converted them into iPSCs and directed them to become RPE tissue. The cells were grown in a single layer, just like they exist naturally. This consists of a biodegradable scaffold designed to promote integration once they reach the retina. Researchers reported their results in Science Translational Medicine.

That protocol “helps ensure that the transplanted cells function reliably and that unintended consequences are minimised,” said Kapil Bhartihead of the NEI Unit on Ocular and Stem Cell Translational Research and the lead investigator for the animal study “[It] also minimises the chance of rejection by developing the iPSC-RPE with an individual’s autologous blood cells.”

One major concern that currently limits iPSC’s therapeutic use in humans is that it can propagate uncontrollably and develop into cancer. The NEI researchers addressed this issue by designing their manufacturing process to avoid cancer-causing mutations.

In animal studies, the scientists reported that their lab-made cells had integrated within the retina 10 weeks after the RPE patches were implanted and safely reversed degeneration of the animals' retinas.

Immunostaining confirmed that the RPE expressed the gene RPE65, suggesting the cell layer had reached a level of maturity necessary to regenerate visual pigment within the photoreceptors. Further tests showed that the implanted RPE cells exhibited ‘phagocytosis’, an essential function that involves trimming the photoreceptors' outer segments to maintain a healthy size.

In addition, electrical pulses recorded from the photoreceptors after the RPE transplant were normal. However, those treated with an empty scaffold, by contrast, experienced photoreceptor death.

In light of the positive preclinical data and robust GMP protocols to make the therapy, the NEI team has started planning for future studies in humans. “If the clinical trial moves forward, it would be the first ever to test a stem cell-based therapy derived from induced pluripotent stem cells for treating a disease,” Bharti said.