Transplant doctors are stepping gingerly into a new world, one month after a Japanese woman received the first-ever tissue transplant using stem cells that came from her own skin, not an embryo.
On Sept. 12, doctors in a Kobe hospital replaced the retina of a 70-year-old woman suffering from macular degeneration, the leading cause of blindness in the developed world. The otherwise routine surgery was radical because scientists had grown the replacement retina in a petri dish, using skin scraped from the patient's arm.
Stem cells have long held great promise for patients with degenerative diseases such as Parkinson's and cancer, which can only be reversed by replacing old tissue with new. But for years, scientists could only use stem cells drawn from embryos. The ethical and religious debates surrounding such potential procedures had hampered stem-cell research for years.
The most exciting thing about the Kobe procedure was that it showed that stem cells made from a patient's skin can be used to create genetically identical replacement tissue, says Dr. Janet Rossant, the chief of research at the Hospital for Sick Children in Toronto and the past president of the International Society for Stem Cell Research.
The Japanese woman is fine and her retinal implant remains in place. Researchers around the world are now hoping to test other stem-cell-derived tissues in therapy. Dr. Jeanne Loring from the Scripps Research Institute in La Jolla, Calif., expects to get approval within a few years to see whether neurons derived from stem cells can be used to treat Parkinson's disease.
Stem cells have two key features: They can divide indefinitely, and they can turn into any other cell type in the body, in what is known as pluripotency.
Pluripotency is a magic bullet for regeneration because it means stem cells can be used to generate replacement body parts. Stem cells drawn from embryos are naturally pluripotent, but are also difficult to use – both because of ethical concerns, and because the immune system often rejects them.
Stem cells from adult tissue solve both problems, but they're not naturally pluripotent. That quality has to be induced.
Seven years ago, Kyoto University's Dr. Shinya Yamanaka figured out how to do that by inserting genes normally found in embryonic stem cells into mature cells, such as those found in skin. The discovery of "Induced Pluripotent Stem Cells" (iPSCs) netted Yamanaka the Nobel Prize in 2012.
Japanese doctors deployed Yamanaka's discovery in last month's age-related macular degeneration (AMD) procedure and five other patients are expected to receive the transplant in the coming months.
AMD occurs when the retina breaks down. The disease, which has no cure, can progress rapidly and is an ideal testing ground for iPS cell therapy.
"If you had to transplant cells, the best place in the body is the eye," explains Dr. Derek van der Kooy, a stem-cell researcher at the Donnelly Centre, University of Toronto. Among other things, retinal transplants are routine, and the eye tolerates grafts of new tissue better than other parts of the body. Retinal cells grow very efficiently too, reducing the chance that the transplant might include any leftover stem cells that could keep growing and cause cancer.
In November, 2013, a team of doctors and scientists led by Dr. Masayo Takahashi at the Riken Center for Developmental Biology (CDB) in Kobe scraped a tiny layer of skin from the patient's arm. They then inserted into the skin cells a cocktail of genes, normally found in embryos, to make them start behaving like stem cells. Next, they used molecular tricks to coax these stem cells to turn on retinal genes and make retinal tissue. It took 10 months to produce the retina that was of a desired quality and safe to transplant. In a two-hour operation, the patient received her new retina and was sent home six days later.
Still, there are significant safety concerns regarding this kind of therapy. Scientists do not fully understand how the introduced stem-cell genes work to turn a skin cell into a dividing iPS cell. While this generates an endless source of stem cells, there is a worry that these dividing cells could turn into cancer. "You only need one stem cell left in the graft that could lead to cancer," SickKids's Rossant warns.
And, in a tragic sidelight, CDB's deputy director killed himself only a few weeks before the procedure, after the centre had to retract two papers published in the journal Nature amid accusations of scientific misconduct. Nonetheless, the Riken Center remains highly regarded for its "fantastic" research, Rossant says.
If found safe and effective, this new treatment for AMD could be widely available in 2020, according to the Riken Center.
The world's stem-cell community is keen to see the next phase of this research.
Scientists across the world are using iPS cells to grow balls of tissue that strikingly resemble organs, such as kidney or liver. The next challenge is to fine-tune these into working organs that could then be used for transplants. This could revolutionize replacement therapy, eliminating organ waiting lists, powerful immunosuppressant drugs and fears of organ rejection.
Dr. Jovana Drinjakovic is a neuroscientist and a Fellow in Global Journalism at the Munk School in the University of Toronto.