Safely Harnessing the Power of Stem Cells

Stem cells are a highly promising treatment approach for a wide range of conditions and diseases, because they can be used to replace virtually any type of cell or tissue in the body lost to disease or injury. In the not-too-distant future, in fact, researchers will be able to turn stem cells into new photoreceptors for people who have lost vision to a retinal disease.

Stem cells can also be used to protect existing photoreceptors by providing the sustained release of beneficial proteins. That is, the transplanted cells can act like a therapy factory built adjacent to the retina.

But stem cells are a two-edged sword. Researchers must carefully harness their power to ensure positive consequences. There are two primary safety concerns with emerging stem cell therapies:

• the development of tumors or other unwanted types of cells
• immunological reactions to the cells when they are transplanted into the eye

While it’s great that stem cells can form any cell type in the body, it’s also a little scary. Scientists need to make sure that a retinal treatment, for example, contains only retinal cells. The worst-case scenario would be that they develop into tumors.

Retinal researchers use proteins to tweak stem cells so that they differentiate into retinal cells or other desired cell types. When they produce stem cells lines, they employ what are fittingly known as Good Manufacturing Practices, or GMP, to ensure that the cells are as pure as possible.

When it comes to preventing an immune reaction to transplanted cells, there is some good news. The eye is considered “immune-privileged,” meaning it’s less susceptible to an attack from the body’s powerful immune system. A barrier comprised of blood vessels outside of the retina is what provides protection. This doesn’t mean there is no risk of an immune reaction — it’s just less than for transplants of other tissues and organs.

While stem cells come from a variety of sources, scientists are particularly excited about induced pluripotent stem cells (iPSC), which are derived from a patient’s mature cells, such as skin or blood. Because the patient serves as his or her own stem cell donor with iPSC, there is less chance of an immune reaction.

At the same time, researchers need to turn a few genes on and off to control which direction cells move in the developmental process. Using proteins to switch these genes on and off, researchers can control whether a cell moves backward in the development process, i.e., a skin cell reverts back to a stem cell state, or a cell moves forward, i.e., a stem cell becomes retinal. This tweaking of genes makes scientists a little nervous about the safety and stability of iPSC, because in some cases it has introduced new mutations. They have wondered if those mutations might cause an immune reaction.

However, a recent report in the prominent science journal Nature has quelled those fears. A Japanese team of researchers found “negligible immunogenicity” of mature cells derived from iPSC and embryonic stem cells.

The first clinical trials of retinal treatments derived from stem cells are being conducted by Advanced Cell Technology (ACT) and StemCells, Inc. The cells used in these therapies are designed primarily to play a protective role in the retina. ACT has reported safety and some modest vision improvement for people with dry age-related macular degeneration (AMD) and Stargardt disease. No reports have come out yet for StemCells, Inc.’s study for people with dry AMD.

The company ReNeuron is tentatively planning to launch its clinical trial of stem cells for people with RP in late 2013.

More stem cell clinical trials for retinal diseases are planned in the coming two to three years, so stay tuned. It is an exciting time in this high-potential field of research.