Scientists working at Novocell, Inc. in San Diego, CA have reported a stunning advance in the race to move embryonic stem cells from the province of basic scientific research into the arena of clinical trials for patients suffering from diabetes. Type I diabetes results from the degeneration of specialized cells in the pancreas (called beta-cells) that produce the hormone insulin. In healthy individuals, a rise in blood sugar after a meal induces beta-cells to secrete insulin, which enables other cells to absorb and utilize the sugar as fuel; when blood sugar levels drop, insulin production is turned down. In diabetics, insulin regulation fails. Currently, patients suffering from this disease have no choice but to constantly monitor blood sugar levels and take insulin shots when those levels rise.
Just a decade ago, it would have been ludicrous to suggest that research in cellular and molecular biology might lead to the development of a laboratory protocol for creating a substitute pancreas that could be implanted into diabetic patients. And yet, the results reported by Emmanuel Baetge and his team at Novocell in the journal Nature Biotechnology suggest that what was once a pipe-dream may soon be a reality -- a long-lasting treatment for diabetes achieved through the use of embryonic stem cells.
Embryonic stem (ES) cells occur naturally within the one-week old human embryo. During normal development not many ES cells are formed, and none stay "embryonic-like" very long. They grow and divide over a few weeks into a variety of more specialized cells that eventually differentiate into every tissue and organ in the adult body. In 1998, however, James Thomson mastered the technology required to isolate ES cells and keep them dividing indefinitely without differentiating in petri dishes. The promise and potential power of ES cell technology lies with scientists uncovering specific molecular signals that would channel ES cells to develop into just a single tissue, which could be used to treat a particular disease.
|One of the cell bunches below is a human embryo, the other is a group of embryonic stem cells. Can you tell the difference? I can't|
The key to the success of the Novocell team was not to go for the gold all at once, but to carefully mimic the natural step-by-step process by which a subset of cells in a human embryo become gradually transformed into a pancreas. This process is driven by a timed sequence of particular genes turning on and off. Baetge and his colleagues recapitulated the entire process in a petri dish, starting with isolated ES cells and channeling them through a series of four intermediate stages, over a two-week period, prior to a final transformation into pancreatic tissue that produces insulin in quantities similar to that produced in a healthy pancreas. Since none of the intermediate stages of pancreatic development survive inside an adult body, the protocol appears absolutely dependent on starting with ES cells, rather than any conceivable adult cell.
The Novocell team is not yet home free. So far, they have produced fetal-like pancreatic tissue that is not responsive to changes in sugar levels. The protocol must be extended one more stage to produce fully functional adult cells. Baetge is confident that this goal will be achieved within the next year. If all goes as planned, he says, clinical trials could begin as early as 2009. At the end of their publication, Baetge and colleagues write, "We are awed by the capacity of hES cells to recapitulate development ex vivo and are optimistic that these unique cells will ultimately represent a renewable source of pancreatic beta-cells for people with diabetes."
In the brief time since human ES cells were first isolated, many opponents of the research have argued vociferously that the potential of this line of research for creating novel therapies has been hyped by scientists. Indeed, even research supporters have been cowed into a hyper-cautious mode, agreeing that it might be decades before the technology provides treatments for common diseases. The Novocell team ignored all of this pessimism and got on with the job. In doing so, they showed that hype can flow both ways.
(Full disclosure: I have no financial interest in this company or any other biotech company. LMS)