Discovery by Buck Institute scientists may speed use of stem cell therapies
By Richard Halstead, Marin Independent Journal
POSTED: 07/05/16

Scientists at the Buck Institute for Research on Aging in Novato have discovered that a protein common to insects, animals and humans may enhance the use of stem-cell-based cell replacement therapies.

The finding is reported in the current issue of the peer-reviewed academic journal Science.

Hopes for stem cell therapies have been high because in theory they could be used to replace virtually any tissue or organ that is injured or diseased. But the integration of stem-cell-generated tissue with host bodies has proved problematic.

“I think we’re getting closer to a point where people are able to use stem cells in the clinic,” said Buck chief scientific officer Heinrich Jasper, who co-authored the scientific paper. “Now you’re getting this other problem, which is that you’re trying to put these cells into a tissue that is either old or diseased. A tissue like this will usually have conditions that are not amenable to regeneration. That is exactly the problem our study attacks.”

The initial breakthrough came in Jasper’s lab, where it was found that the protein — Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) — was secreted by the immune cells in flies in response to damage to their retinas and then later acted on the same cells to promote their transition from pro-inflammatory to anti-inflammatory repair cells, promoting retinal repair.

“What we found is that this factor creates a better environment, which helps the tissue repair itself,” said Deepak Lamba, a Buck faculty member who co-wrote the paper with Jasper.

Later the Buck researchers repeated the experiment using mice and obtained the same result.

Lamba said scientists in the past have successfully transplanted retinal stem cells in mice; however, only about 1 percent of the transplanted cells survived and integrated over time. When the researchers used MANF as a supplement while transplanting the retinal stem cells into congenitally blind mice, the efficiency of the cells’ integration increased and the visual function of the mice improved.

“It is actually surprising that you have similar mechanisms controlling tissue repair in the retina of a fly and a mouse. These are quite different tissues,” Jasper said. “This seems to have been a mechanism that developed early in evolution and so even in these very far apart species you have the same response.”

Lamba said, “For the mouse studies, we actually used the human version of the protein, and it still had an effect on the mice. So it is very likely it will have the same effect in humans.”

The discovery could lead to successful stem cell replacement therapies in degenerative diseases of the retina, including age-related macular degeneration. And there is reason to suspect that MANF might assist in using stem cell therapy to treat a range of other illnesses.

“The idea is this process would be happening in all the different tissues so it should work in other tissues as well,” Lamba said.

Chronic inflammation, which MANF helps to suppress, is the hallmark of age-related diseases, such as rheumatoid arthritis, Jasper said.

“The ability to shut down this inflammatory response is not well maintained as we age,” he said. “Focusing on immune modulation to promote a healthy repair response to tissue damage rather than a deleterious inflammatory response is a new frontier in aging research.”

A paper published in the journal Cell Stem Cell last week by scientists at the University of California at Davis shows how eager the public is for stem cell therapies to live up to their potential. The UC Davis scientists reported that 351 U.S. businesses are engaged in direct-to-consumer marketing of stem cell interventions offered at 570 clinics. The scientists said many cosmetic surgery clinics even advertise such procedures as “stem cell facelifts” and “stem cell breast augmentation” in addition to sexual enhancement procedures.

They write in their paper: “Many of these marketing claims raise significant ethical issues given the lack of peer-reviewed evidence that advertised stem cell interventions are safe and efficacious for the treatment of particular diseases.”