Recently, news swept the world that Harvard scientist Dr. Douglas Melton and his team have developed a lab technique that can transform not-fully-developed human stem cells into billions of new insulin-producing beta cells. This news was greeted with cheers, as scientists have been struggling for years with how to find a way to grow beta cells in bulk. Scientists want more beta cells so they can transplant the cells into people with Type 1 diabetes to restore pancreatic function. Some breathless news stories even hailed Dr. Melton’s findings as a cure.
Patient questions came pouring into the inboxes of endocrinologists. Patients asked me: What does this mean? Is this a cure? What are the next steps? How do I get my new beta cells? How long will they last?
I highly commend Dr. Douglas Melton, who has a deep commitment to the field of diabetes research. His previous work has been very instructive in understanding the fact that new beta cells form primarily from existing beta cells in adults. The data of Dr. Melton’s study is extraordinarily interesting, and his techniques are novel.
Currently, scientists have struggled with how to grow beta cells in a timely fashion, and beta cell therapy requires a lot of beta cells, as many islets die during the transplantation process, or soon after transplantation. We learned many lessons from undertaking islet transplants in the past several decades, but we have not been successful in making islet transplant a viable treatment for Type 1. Despite employing immunotherapy to protect transplanted islets from the body’s attack, patients still end up requiring multiple transplants. One major problem is that transplanted cells are inserted into the liver, not in the pancreas, and the liver isn’t as well equipped for such an islet transplant. Islets are high maintenance, requiring 20% of the blood flow to the pancreas, despite making up only 2% of pancreatic cells. Beta cells belong inside islets and islets belong in the pancreas, and that’s why the technique has had a high failure rate. Islet transplantation has been discontinued at most centers.
More beta cells open up many new potential opportunities in regenerative medicine for diabetes. Dr. Melton even demonstrated that the beta cells made could sense glucose in mice; previous researchers using the same type of stem cells to grow beta cells were unable to get the beta cells to function properly.
Dr. Melton’s work builds on the work of earlier pioneers in the field of diabetes regenerative medicine. For example, Dr. Nancy Parenteau demonstrated more than a decade ago the potential for engineering new islets from adult stem cells found in the pancreas. Drs. Lawrence Rosenberg and Aaron Vinik also have shown the ability to accelerate this process of transforming ductal cells that surround the islet into new islets without the use of transplantation. Rosenberg and Vinik at one point were successful in using this treatment to help Type 1 patients make a significant amount of their own insulin again without the need for transplantation of beta cells or islets.
This study did not use an immune protectant, however, and the benefits were short lived. Unfortunately, creating new insulin-producing beta cells housed within fully functional islets is only half of the equation for Type 1 diabetes. The other half is preventing the autoimmune attack of the body on the new insulin-producing cells. Many new diabetes therapies are in development, including the delivery of encapsulated embryonic stem cells that may even be immune protected. For decades, scientists have designed hundreds of types of implantable devices to hold beta cells and protect them from immune attack. The first ones resembled a hockey puck that would be implanted in the abdomen. Over time, the implantable devices have gotten smaller and more sophisticated. We hold out hope for new methods of encapsulation of beta cells that can release insulin, yet be protected from immune attacking cells.
The next step for Melton’s breakthrough will be to have other teams reproduce the results. Studies then will be conducted in animals to determine if these beta cells from the dish can be successfully transplanted into man. The questions researchers hope to answer include:
- How long will the transplants last?
- What immunotherapy will be needed to prevent autoimmune attack?
- In what way will these beta cells function differently than their predecessor cells?
Perhaps the best part of Melton’s breakthrough is that it has the potential to provide scientists with much more raw material to work with to explore regenerative medicine in diabetes. Readily-made beta cells may provide a wonderful new treatment option for the future, and it may be a window into newer discoveries that we hope will make diabetes a treatable disease without the use of insulin.
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