Diabetes occurs when the body fails to manage its blood glucose levels. A type of diabetes where the body cannot make insulin in any respect. Called Type 1 diabetes, or T1DThis autoimmune disease occurs when the body's immune system mistakes its own insulin-producing cells as foreign and kills them. On average, T1D can lead patients to Lose an average of 32 years of healthy life.
Current treatments for T1D include Lifetime insulin injections. Although effective, patients taking insulin are susceptible to low blood glucose levels, which might cause symptoms resembling tremors, irritability, hunger, confusion and dizziness. Severe cases may lead to seizures or unconsciousness. Real-time blood glucose monitors and injection devices may also help prevent low blood sugar levels by controlling insulin secretion, but they Do not work for some patients..
For these patients, a treatment is known as for Islet transplantation They may also help higher control blood glucose by giving them each latest insulin-producing cells in addition to cells that prevent glucose levels from getting too low. However, this is restricted by donor availability and the necessity to use immunosuppressive drugs. Only 10% of T1D patients are eligible for islet transplant.
In my work as a Diabetes researchermy colleagues and I actually have found that creating islets from stem cells may also help overcome the challenges of transplantation.
History of islet transplantation
There was islet transplantation for type 1 diabetes. FDA approved in 2023. After greater than a century of investigation.
Insulin-producing cells, also called beta cells, are situated in areas of the pancreas called Islet of Langerhans. They are present in clusters of cells that produce other hormones involved in metabolism, resembling glucagon, which increases blood glucose levels. somatostatin, which inhibits insulin and glucagon; and ghrelin, which signals hunger. Anatomist Paul Langerhans discovered the islands. In 1869, while studying the microscopic anatomy of the pancreas, observed that these cell clusters stained distinctly from other cells.
The path to islet transplantation has faced many obstacles because it was first hypothesized by pathologist Gustave-Edouard Lagos. Islet plays a role in hormone production. At the top of the nineteenth century. In 1893, researchers tried to treat a 13-year-old boy dying of diabetes. Sheep pancreas transplantation. While they saw a slight improvement in blood glucose levels, the boy died three days after the procedure.
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Interest in islet transplantation was renewed in 1972, when scientists Paul E. Lacy Islets were successfully transplanted into diabetic mice. after that, Many research groups Islet transplantation has been attempted in humans, with no or limited success.
In 1999, transplant surgeon James Shapiro and his team successfully transplanted islets in seven patients in Edmonton, Canada, by concurrently transplanting numerous islets from two to 3 donors and using immunosuppressive drugs. of through The Edmonton Protocolthese patients were capable of manage their diabetes without insulin for one yr. As of 2012, More than 1,800 patients have received islet transplants Based on this system, and roughly 90% survived through seven years of follow-up. gave First FDA-approved islet transplant therapy Based on the Edmonton Protocol.
Stem cells as a source of islets
Islet transplantation is now considered a minor surgery, where islets are inserted into the hepatic vein through a catheter. As easy as that sounds, there are. Many challenges related to the procedure, including its high cost and limited availability of donor islets. Transplantation also requires lifelong use of immunosuppressive drugs that allow the foreign islets to live and performance within the body. But using immunosuppressants also increases the chance of other infections.
To overcome these challenges, researchers are using stem cells to create a vast source of islets.
are Two types of stem cells For islet transplants, scientists are using: embryonic stem cells, or ESCs, and induced pluripotent stem cells, or iPSCs. Both types will be matured in islets within the lab.
Each has benefits and drawbacks.
There are ethical concerns about ESCs, as they're obtained from dead human embryos. Transplantation of ESCs would still require immunosuppressive drugs, limiting their use. Thus, researchers are working to either encapsulate or mutate ESC islets to guard them from the body's immune system.
In contrast, iPSCs are obtained from the skin, blood or fat cells of a patient undergoing transplantation. Because the transplant involves the patient's own cells, it bypasses the necessity for immunosuppressive drugs. But the fee of making iPSC islets for every patient is a significant hurdle.
Stem cell islet challenges
Although iPSCs could theoretically avoid the necessity for immunosuppressive drugs, this approach must be tested within the clinic.
T1D patients who've genetic mutations that cause the disease cannot currently use iPSC islets, since the cells that might be taken to make the stem cells will even carry the disease-causing mutation of their islet cells. can take Many available gene editing tools Can possibly be removed They produce mutants and functional iPSC islets.
In addition to the challenge of genetic adaptation, cost is a significant issue for islet transplantation. Transplantation of islets constructed from stem cells is costlier than insulin therapy due to high cost. Manufacturing costs. Efforts to reinforce the method and make it less expensive include innovation. Biobanks for iPSC matching. This would allow iPSC islets for use for multiple patients, reducing costs by avoiding the necessity to create freshly modified islets for every patient. Embryonic stem cell islets have the identical advantage, as the identical batch of cells will be used for all patients.
These stem cell islets are also susceptible to developing tumors after transplantation. to date, Laboratory studies on rats And Clinical trials in humans Rarely any cancer has been shown. This suggests that these cells are less prone to turn into tumors.
That being said, several rounds of research and development are needed before stem cell islets will be utilized in the clinic. It's an arduous journey, but I consider a number of more improvements could help researchers beat diabetes and save lives.