John Farrell is a science and technology blogger for Forbes online. John was invited to cover proceedings at the 2015 Till & McCulloch Meetings and this is his first report. This blog also appears on Forbes and is reprinted here with permission.
Timothy J. Kieffer and his team of researchers at the University of British Columbia were recently awarded the prestigious 2015 Till & McCulloch prize in recognition of a breakthrough paper they published detailing a promising way to mass produce insulin secreting cells for patients with Type 1 diabetes.
The annual Till & McCulloch conferences meet in the Fall, sponsored by the Centre for Commercialization of Regenerative Medicine, the Stem Cell Network, and the Ontario Institute for Regenerative Medicine.
This year’s meeting, which I attended, took place in Toronto, where Kieffer headlined a number of outstanding Canadian researchers presenting their labs’ latest findings. Considering that stem cells were first discovered by Canadian scientists, Drs. James Till and Ernest McCulloch in the early 1960s, the sponsors take a great deal of pride in showcasing the country’s cutting edge programs. And indeed, most of the seats in the main presentation hall were filled day in and day out by the scientists in attendance, many of whom, I note, were quite young and from all across Canada (with many visitors from the U.S., Europe, and Asia as well).
Like their counterparts at Douglas Melton’s lab at Harvard, Kieffer and his team have zeroed in on how to generate insulin-producing cells from human pluripotent stem cells (specifically embryonic stem cells).
The work was cited as a notable advance in 2014 by Nature Medicine and along with the similar work published subsequently in Cell by the Melton lab, was runner up for the journal Science’s breakthrough of 2014 (the winner was Rosetta Mission’s Comet Landing).
What’s interesting about Kieffer et al’s work is that the cells they generated are not beta cells, the insulin producing cells that reside in the normal pancreas. In patient’s with diabetes, beta cells are attacked by the body’s own immune system, preventing control of glucose in the blood stream, leading to multiple debilitating complications such as obesity, blindness, heart disease, kidney failure, and more.
Kieffer Lab’s insulin-producing cells were derived in a seven-stage process, according to the paper Kieffer’s team published in the November 2014 issue of Nature Biotechnology. Their so-called Stage 7 cells “expressed key markers of mature pancreatic beta cells,” and also displayed glucose-stimulated insulin secretion similar to that of human islets of beta cells during static incubations in vitro.
Further analysis, they reported, revealed similarities but also notable differences between their S7 insulin-secreting cells and primary human beta cells. “Nevertheless,” they wrote, “S7 cells rapidly reversed diabetes in mice within 40 days, roughly four times faster than pancreatic progenitors.”
When I reached Keiffer by email, he was effusive about this team’s collective effort. “I accepted this award on behalf of a large number of individuals who did the work, including several members of my laboratory and that of my colleague Dr. James Johnson at the University of British Columbia, and scientists from the New Jersey company BetaLogics under the leadership of Dr. Mark Zimmerman. Our paper’s lead author, Dr. Alireza Rezania, is the mastermind behind the development of this new protocol.”
What are the next steps? Are S7 cells ready for testing in humans? Keiffer hopes to advance this work to clinical trials in patients with diabetes.
“In this regard,” he reported, “it is encouraging that FDA and Health Canada have already approved clinical trials by the company ViaCyte for the transplant of stem cell derived pancreatic cells into patients, which paves the way for additional cell therapy trials.”
A major challenge facing all cell therapies for diabetes, is preventing the patient’s already misguided immune system from destroying the ‘newcomers’. But immunosuppression drugs can cause long-term complications for the patient.
Kieffer said he would like to develop a cell-based therapy for diabetes that does not require any form of immunosuppression for the patients.
“We are exploring how well the differentiated cells survive and function following transplant under the skin within devices that are designed to protect the cells from immune attack,” he told me.
In addition, his lab also continues to look at ways to improve the ease and efficiency of their S7 recipe for cell differentiation, with a view towards mass production of cells for wider treatment of patients as clinical trials go forward.
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