Scientists focus on curing blindness.
Want to see the future of stem cell science? Look in the mirror.
See the retina – the thin black line outside the iris? Those are retinal pigment epithelial (RPE) cells. And that’s where the stem cell revolution in new treatments likely will begin.
Outstanding advances in treating leukemia, multiple myeloma and other blood-borne cancers notwithstanding, stem cells have yet to deliver the kind of treatments and cures many had hoped would be available by now. That is soon to change. Not in the blink of an eye, but certainly over the next few years.
“I think that blindness is going to be the first disease cured using pluripotent cells,” says Dr. Derek van der Kooy of the University of Toronto.
Dr. van der Kooy, whose team discovered retinal stem cells 13 years ago, bases his prediction on the fact that the retina is an easy target.
“It’s well laminated and there is this fantastic sub retinal space where you can inject the cells perfectly, exactly where they are supposed to go,” says Dr. van der Kooy. “You can actually see what you’re doing – you can look in the eye and see where you’re injecting the cells. With the heart or the brain, you can’t see where they (the stem-cell-derived transplant cells) are going. Also, it’s an incredibly sensitive assay to see whether they work or not: you can see whether vision improves.”
Dr. van der Kooy’s comments come in the wake of Japan’s announcement that it has approved the world’s first human tests using induced pluripotent stem (iPS) cells. They will be used to produce RPE cells to treat age-related macular degeneration.
Japan’s Dr. Shinya Yamanaka first demonstrated how to create iPs cells in 2006 (in mice) and 2007 (in humans). Essentially, he came up with a process to take adult skin cells and induce them into becoming pluripotent (capable of differentiating into any cell the body needs) much like human embryonic stem cells. It was an amazing feat for which he won the 2012 Nobel Prize in Physiology or Medicine.
The discovery of iPS cells created a whole new source of pluripotent stem cells and, perhaps more significantly, got around ethical concerns about destroying embryos left over from in vitro fertilization to create embryonic stem cell lines.
But there was a problem. Dr. Yamanaka‘s original method used viruses in the reprogramming process, creating a risk of causing mutations and triggering disease. Other researchers, notably Dr. Andras Nagy at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, have since devised other, non-viral ways of creating the cells to avoid that risk.
Japan invests $1 billion in iPS cells
Clearly, Japan thinks any risk is now negligible. The Wall Street Journal reported in late June that Japan has committed more than $1 billion over the next 10 years to advance iPS cell research and develop clinical applications. The age-related macular degeneration trial – involving just six patients – represents, the WSJ reports, “a big step forward [for Japan] in the race to develop stem-cell therapies.”
Dr. van der Kooy, however, points out that an American company, Advanced Cell Technologies, is already conducting clinical trials to test the safety of RPE cells derived from embryonic stem cells as a therapy for age-related macular degeneration and Stargardt disease (a juvenile form of the condition).
“It is the very first time that people have used iPS cells to try to treat a disease in humans, but conceptually it’s not that different than the ACT trial going on in the States right now,” says Dr van der Kooy. “And there are two other embryonic-stem-cell-derived trials that are going to start: another one in California and one in England. All four will be essentially the same type of trial – attempts to make RPE cells from pluripotent human cells for either macular degeneration or Stargardt’s.”
There is also a potentially crucial Canadian connection to this story. Dr. Molly Shoichet, a bioengineer and colleague of Dr. van der Kooy at the University of Toronto, has developed a stem cell delivery system that uses a minimally invasive and biodegradable gel called HAMC (pronounced “hammock”) to deliver the progenitor cells to the retina.
“We’ve seen a pro-survival effect in the lab tests and in animal models,” says Dr. Shoichet. “The cells survive better when we deliver them with the gel and they integrate better in the retina.”
So the race is on to cure blindness caused by macular degeneration using with iPS cells and embryonic stem cells. “When you think about it, it’s the general argument for stem cell biology,” says Dr. van der Kooy. “Once cells have degenerated, the only way you’re going to improve them is replace the cells you’re missing.”