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Some may think that it should be easy to cure diabetes: all you'd need would be an endless supply of islets, the pancreatic cells that produce insulin, to be transplanted into people with diabetes. But there are not nearly enough donated organs to go around, and, because the donated pancreas is actually someone else's organ, transplant patients need to take anti-rejection drugs for the rest of their lives.
Wouldn't it be ideal to find a therapy that used your own cells to cure you? New stem-cell therapies could be bringing that hope closer to reality than ever.
Scientists have made breakthroughs on many fronts and have their sights set on creating customized insulin-producing cells on demand.
Where Do Stem Cells Originate?
If stem cells are magical, however, they are also scarce.
For diseases in which the attack on the body is continual—like diabetes—there may not be enough stem cells to keep up with the damage. It would be ideal if researchers could simply extract one of your adult pancreatic stem cells and culture it in a petri dish. When it multiplies, they could inject these cloned cells back in to reinforce the local troops. Unfortunately, adult stem cells—like most human cells—are difficult to culture. After 50 divisions or so, they die.
Not so for embryonic stem (ES) cells, which are virtually immortal and can be cultured indefinitely. That is why the field is so important right now and has caught the attention of the mainstream media as well as the president of the United States.
But where do you find ES cells? Try as they might, the only way research-ers have ever been able to grow ES cells involves an egg. No amount of lab equipment has been able to mimic the complex environment provided by an egg.
One obvious source of ES cells is blastocysts—embryos at the 16- to 64-cell stage of development—created as part of medical procedures to treat infertility.
Typically, these procedures produce more fertilized eggs than can be implanted in the prospective mother. Fertility clinics typically either freeze or destroy the surplus. Or, if the donor approves, the eggs can be used to create stem-cell cultures.
The blastocyst is only days old and, with only 16 to 64 cells, has no defined tissues. Some people, however, consider the destruction of a blastocyst to be equivalent to abortion, a position that has frightened many people away from this field of study.
A new and ethically less challenging procedure is to use the patient's own DNA to create stem cells. This technique uses unfertilized eggs, which most religious authorities do not consider to be unique human beings. The procedure, called nuclear transfer, takes the DNA out of the egg and replaces it with DNA from the patient. Even though it hasn't been fertilized, the egg can be tricked into dividing and forming a blastocyst with a tiny electrical pulse. At the blastocyst stage, the stem cells are harvested and cultured. These cells can then be injected as a "liquid transplant" to treat all sorts of diseases. Since they carry the patient's own DNA, no rejection problem develops.
Potential Treatments for Type 1 Diabetes
Given these new techniques, one possibility for treating type 1 diabetes might be to provide islets derived from their own tissue to people with diabetes. But type 1 diabetes is a disease of the immune system, which targets islets for destruction. If you simply put a type 1's own islets back into the body, won't the immune system just wipe them out again?
To solve this problem, one line of research aims to genetically engineer these cell cultures so that the immune system won't notice them. The islets found in people with type 1 have markers that improperly identify them as targets for destruction. The idea is to delete the genes that create these markers. Once these genes have been excised, the "unmarked" cell is cultured.
These ES cells are then treated with special proteins that convert them to pancreatic stem cells, still based on the patient's own DNA. Once injected, these cells should repair the pancreas while avoiding destruction by the immune system—completely curing the disease.
Alternatively, as in some cancer therapies, another technique might be to harvest a few stem cells, destroy the immune system with radiation or chemotherapy and then restart the immune system with the harvested cells. Research by Richard Burt, MD, of Northwestern University suggests that once the immune system is renewed, it starts from scratch and no longer attacks the body.
Potential Treatments for Type 2 Diabetes
Type 2 diabetes usually develops later in life than type 1, and it afflicts 10 times as many people.
Type 2 can sometimes be managed with diet and exercise, but it often progresses to the point where oral medications or insulin therapy are needed. Type 2 diabetes involves a defect in the islets of the pancreas, in addition to insulin resistance (the body's inability to utilize insulin properly).
If, as suspected, a genetic flaw lies behind type 2 diabetes, it might be possible to use genetic engineering to repair the defective gene. The corrected stem cells would be cultured and transplanted back into the patient. Since the stem cells are persistent and can produce islet cells as needed, the person with diabetes might look forward to a complete cure with a single injection.
Researchers at the Whitehead Institute in Cambridge, Massachusetts, recently demonstrated the feasibility of such a procedure using mice with a deadly genetic defect. ES cells were created for each mouse using nuclear transfer, and the "broken" gene was then repaired in the lab. After culturing, these cells were injected back into the mice. The transplanted stem cells quickly took hold and cured the mice.
As well as holding out the promise of outright cures, stem cells offer the potential to help treat the secondary diseases of diabetes, such as heart, kidney, eye and circulatory ailments. Stem-cell scientists, promising longer and healthier lives for all people with diabetes, are targeting each of these diseases for research.
The scenarios envisioned for stem-cell treatments are not without medical risk. The proposed techniques are very new, and researchers are also concerned with ways to prevent stem-cell development from going awry.
Because they can give rise to any of the body's cells, stem cells have sometimes been implicated in the development of teratomas. These are tumors or cysts that can contain inappropriate bits of tissue—from various skin layers, other organs, even bits of hair and tooth tissue. They are often benign, but they can cause a multitude of problems, and a small percentage can become malignant.
Another major worry about stem-cell research is how to stop stem cells from stepping over the line and proliferating beyond the target goal. So far, such proliferation remains a rare side effect, but it points up the necessity for further research.
Editor's note: We are aware that many people are anxiously awaiting treatments that could reverse their diabetes. It is thus important to note that this research is still in its very early stages.
1 comment - May 1, 2002
Diabetes Health is the essential resource for people living with diabetes- both newly diagnosed and experienced as well as the professionals who care for them. We provide balanced expert news and information on living healthfully with diabetes. Each issue includes cutting-edge editorial coverage of new products, research, treatment options, and meaningful lifestyle issues.