Stem cells that stay

Retinal stem cell transplants in mice have been successfully boosted with one of the body’s own immune system proteins – and the next step is human stem cells.

Buck Institute, California, assistant professor, Dr Deepak Lamba, told OT that one major problem holding back human stem cell transplants for conditions like macular degeneration (MD) is that the replacement cells struggle to integrate into the original tissue, and few survive.

However, Dr Lamba’s team has discovered an immune system protein that could change this.

This protein – Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) – converts inflammatory immune cells into ones that repair tissue.

After first studying the protein in the eyes of flies, the researchers turned to congenitally blind mice to see what effect MANF might have during a stem cell transplantation. The protein was given to the mice in intravitreal injections, Dr Lamba said.

MANF meant that the newly introduced photoreceptor cells more successfully integrated into the sub-retinal space, and the visual recovery of the animals was significantly improved, he outlined, adding: “The functional improvement in congenitally blind mice really thrilled the team.

“This is the first study to look at MANF in the retina and as an immune modulator. We are next looking to confirm its potential in human cell replacement therapies,” he emphasised.

Dr Lamba highlighted that the first use of the natural protein as a human therapy may be for early-stage MD treatment, using MANF to protect against photoreceptor loss as the disease progresses.

His team is currently exploring this, as well as how MANF affects the body outside of the retina.

Dr Lamba said that the use of MANF injections alongside stem cell transplants was a process that is likely to take a longer time to be approved for use in patients with MD. “[It] is somewhat complicated as it requires studies to satisfy regulatory authorities for both the photoreceptor cells as well as [MANF],” he explained.

MANF had been studied by other scientists for its role in conditions like Parkinson’s disease, Dr Lamba noted.

Image credit: Buck Institute for Research on Ageing