The stem cell therapy’s obstacle course

Author: Jovana Drinjakovic, 08/25/16
A retinal graft in a dish. The tissue was grown from skin cells, scraped off a patient’s arm, after they were reprogrammed into stem cells. (Credit: RIKEN)

A retinal graft in a dish. The tissue was grown from skin cells, scraped off a patient’s arm, after they were reprogrammed into stem cells. (Credit: RIKEN)

Science fiction became real life in September 2014, when a team of eye surgeons in Japan transplanted a body part, grown entirely in a dish, into the eye of a patient suffering from an eye disease. The retinal graft came from the patient’s skin cells, raising hopes that one day our own bodies could be used to grow replacement organs when needed. The procedure came at the speed of light, only eight years after Professor Shinya Yamanaka, of Kyoto University, made stem cells in a dish.

But the second patient’s transplant — part of a clinical trial testing the procedure’s safety — had to be stopped after genetic changes, or mutations, were discovered in his cells, raising safety concerns.

After a year of hiatus, the trial is back on track, albeit with a twist: the transplant tissue will be made from stockpiled cells, collected from healthy volunteers, instead of patients’ own cells. While using cells from strangers runs against the idea of a personalized treatment, it’s supposed to make stem-cell therapy both safer and economical.

Stem cells can turn into any cell type in the body, and as such hold great promise for making replacement tissues. They occur naturally in embryos, but collecting them has been mired in controversy. The breakthrough came in 2006 when Yamanaka successfully reprogrammed adult skin cells to become stem cells, for which he was awarded the Nobel Prize in 2012.

The finding opened the door to a new era of stem-cell therapy, in which replacement tissue could be created directly from a patient, dealing in one stroke with the fear of immune rejection and the controversial use of human embryos.

The pace at which these personal reprogrammed stem cells reached the clinic was unprecedented. But the scare over the second patient’s mutations called for a change of strategy. This is not unusual: conducting research is like navigating an obstacle course, except that most obstacles are invisible. “Sometimes you have to stop, go back and figure out the problem,” says Dr. Valerie Wallace, a stem cell researcher at the University Health Network in Toronto.

It remains unclear if the mutations were caused by reprogramming, which is known to cause genome instability, or if they occurred by chance, perhaps even before the patient enrolled in the study. Some mutations we’re born with. Others creep into the genetic material inside our cells as we get older. Most of them are harmless, but some people end up with more genetic damage than others. For them, a graft derived from their own cells would not be advisable as the mutations could spur the cells to multiply out of control and become cancer.

One way to avoid this is to use cell banks containing stem cells from a small number of mutation-free donors and collected to immuno-match the majority of the population. The economics of it are better too, because a tiny amount of one person’s cells could be used to make not only retinal, but also, for example, heart, lung or brain transplants, to treat a large number of people with different diseases. What’s more, the patients would have an immediate off-the-shelf supply of cells without having to wait for months to have their own stem cells created.

Donors’ cells are already being collected at Kyoto University’s Centre for iPS Cell Research and Application (CiRA), headed by Yamanaka. Cells collected from 140 donors, representing the most common immune types, could potentially be used to treat more than 90 per cent of the Japanese people, Yamanaka said in an interview in The Japan News, excerpts of which are available on Dr. Paul Knoepfler’s blog.

Immune-matched cell banks also being considered in North America, but setting them up will be challenging because of the greater genetic diversity in the population.

What’s unclear is if the immune-matched donor cells will stop transplant rejection. Patients may still need to take drugs to squash their immune systems, with potentially serious side-effects. In the same interview, Yamanaka hints at the banked cells being only a temporary solution. The emerging gene-editing technologies should be able to correct any genetic errors in patients’ cells and, as cell reprogramming becomes safer, I think we’ll see a return to a personalized stem-cell therapy.

For now, the pioneering trial is moving on with the retinal tissue grown from banked cells. The first transplant is scheduled for early 2017 when all eyes will be on Japan again, watching history being made.

My post is part of Signals’ first-ever blog carnival and we’re recognizing the 10-year anniversary of iPSCs. Please click here to read what other bloggers think about this.

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Jovana Drinjakovic

Jovana Drinjakovic

Jovana Drinjakovic is a science writer with a background in cell and developmental biology. After completing her PhD in Cambridge (the old one) and a postdoc at the Hospital for Sick Children in Toronto, Jovana decided to switch gears and enrolled into a journalism course at the University of Toronto’s Munk School of Global Affairs. Her writing appeared in the Globe and Mail, the National Post, Dallas Morning News and U of T Magazine. Most days Jovana writes about discoveries at U of T’s Donnelly Centre, where she works as a communication specialist.
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