Saturday, May 19, 2007

Human Embryonic Stem Cells Cultured Into Pancreatic Beta Cells

On Thursday, May 17, 2007, a private company known as Geron Corp., which is based in Menlo Park, CA (near Stanford University) reported that they had successfully transformed human embryonic stem cells into the pancreatic beta cells. Earlier research was able to successfully culture beta cells in vitro, but those cultured beta cells did not properly release insulin in response to glucose. In Genron's lab dishes, the cultured cells produced insulin, glucagon and somatostatin, three of the major hormones produced by islet cells.

It is now fairly is well-established that islet transplantation, which can potentially be done on an outpatient basis by infusing beta cells into the patient's portal vein, can restore insulin independence, at least temporarily. The early results using the Edmonton Protocol first conducted back in March 1999, avoided the use of steroids which have proven toxic to beta cells. The Edmonton Protocol used cadavor beta cell tissue which were transplanted into the patient's liver (as opposed to the pancreas), but the procedure required lifelong use of immunosuppressants, whose long-term usage is suspected (although few studies have proven this) of causing certain types of cancer. And the limitations of that protocol are now better understood.

For example, we know that the procedure was most successful when more cells were transplanted, but there are simply not enough cells available for transplant to benefit all patients with type 1 diabetes, let alone some of the type 2 patients who could also benefit. Perhaps most notably, sustained insulin independence was not achieved in most patients, although the transplanted islets still function enough to provide protection from severe hypoglycemic episodes and unawareness, which is common among patients with type 1 (far less common among patients with type 2). However, if cells could be cultured in vitro, then the supply issue could be resolved, and its possible that recurring transplants could resolve the issue.

The basic idea is that genetically identical pancreatic beta cells could be grown in tissue culture with use of a donor nucleus from a patient and human embryonic stem cells, thus enabling the beta cells that are destroyed by the body's immune system in type 1 diabetes to be replaced without the need for toxic immunosuppressants. That, theoretically, could be combined with another therapy to arrest the immune system attack on the beta cells, restoring insulin independence. For example, it has been proven that short-term treatment with monoclonal antibodies has arrested the autoimmune attack in recently diagnosed type 1 patients.

Opponents of stem cell research have remained fairly quiet since earlier this month it was revealed that researchers discovered to their surprise, that adult stem cells -- which they had expected to play a crucial role in beta cell generation -- played no role in the process. Whether these latest results yield anything substantial for patients with diabetes in the immediate future remains to be seen. But its fair to say that private enterprise, which remains free of Federal funding restrictions, occurred in spite of the President's restrictions on embryonic stem cell research, not because of it.


BetterCell said...

As you stated, adult stem cells did not elicit the growth of Beta Cells and long term Immuno-suppression is toxic as well as having other problems associated with it on a functional level.
For those of us with a history of already established T1DM, there really is nothing as far as "successful" transplantology goes. Either it is short-lived(insulin independence) or does not work.
The problem to be solved goes back to the start line again......

concerned heart said...

People should also know that later paternal age past 32 is a risk factor for de novo diabetes in ones offspring.

Scott said...

Sounds a lot like all of diabetes research since 1922, doesn't it?!

I think the reality is that the medical profession has consistently underestimate this disease. The continued fixation and the never-ending quest for achieving perfect glycemic control, they've lost site of the condition's basic etiology ... its all about fixing the immune system, an area that remains under-funded.

In terms of paternal age, the evidence is mounting that there is risk for a variety of diseases, but the point is largely irrelevant to most people who are affected, as its too late to prevent these problems once they occur. (Personally, both of my parents were in their early 20's when I was born, age was not a factor.)

There are 80 other autoimmune conditions out there share a common problem with a faulty immune system, yet not one of these conditions has ever been cured. Ideally, we should be working together to encourage a collective approach to the issue. That's one reason I support the efforts of the American The Autoimmune Related Diseases Association. The NIH has finally started to look at this issue collectively, and released results to its first report chaired by the National Institute of Arthritis and Musculoskeletal and Skin Diseases back in 2005 (see Progress in Autoimmune Diseases Research, Report to Congress for details).

Emily said...

"In Genron's lab dishes, the cultured cells produced insulin, glucagon and somatostatin..."

Does that mean that these islet cells were not producing amylin?

Scott said...


What it means is that the cultured beta cells were the first to successfully produce those hormones, whereas previous efforts to culture cells that produced even insulin failed. Its not clear based on the data that has been released whether amylin was measured, but we do know that that particular hormone is released at a comparatively low ratio relative to the other hormones, so its possible that the presence of amylin may not have been detected, but that question is best directed towards Genron.

arif said...

I agree with Scott

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