Type 1 Diabetes (T1D), also known as juvenile or insulin-dependent diabetes, is a chronic medical condition in which the pancreas is unable to produce a sufficient amount of insulin. This disease is often referred to as “juvenile diabetes” because it is mainly found in children and adolescents. Different factors, including genetics and viruses (such as rotavirus and mumps) can trigger the onset of T1D. Symptoms include increased thirst, frequent urination, unintended weight loss, fatigue, blurred vision, and more. Although there have been many efforts to develop a treatment for this disease, there are no known cures to this date. Over time, constant levels of high blood sugar can lead to damage of the blood vessels, leading to the deterioration of major organs such as the heart and kidneys, and other parts of the body such as the eyes and nerves (Mayo Clinic, 2017.).
The Importance of Insulin
Insulin is a hormone produced by the pancreas that allows your cells to use glucose from carbohydrates in the food you eat for energy or to store it for future use. This hormone plays a vital role in ensuring a stable blood sugar and homeostatic environment within the human body. The cells in our body need glucose as energy to carry out cellular functions, but this glucose cannot simply enter our cells; the insulin hormone is necessary in “unlocking the cell” so that the insulin can enter, which is why insulin is oftentimes referred to as a “key” (Fischl, 2019). Insulin is produced in the pancreas, specifically in the Islets of Langerhans cells, or more simply, islets cells. There are three different types of islets cells, however the beta cells are what produce the hormone insulin specifically (Bowen, n.d.). In T1D patients, these beta cells are damaged due to autoimmune response, therefore these patients are unable to produce insulin. This condition is different from the more commonly seen Type 2 Diabetes (T2D). T2D patients are able to produce insulin, but their cells do not react to its efforts to allow glucose into them (Fischl, 2019). To summarize, T1D patients are unable to produce the “key,” whereas T2D patients have the key, but are unable to use it because it is broken.
Current Treatments for T1D
The most commonly used treatment for T1D is an injectable form of insulin that helps temporarily control blood sugar. These treatments must be given as an injection rather than in pill form because the stomach acids would break the hormone down to levels where it is ineffective in controlling blood sugar levels. The four basic categories of insulin include rapid-acting insulin (works 15 minutes after injection, lasts for 3 hours), short-acting insulin (works an hour after injection, lasts for 7 hours), intermediate insulin (works 2 hours after injection, lasts for 15 hours), and long-acting insulin (works 2 hours after injection, lasts for 24 hours) (Fischl and Marsh, 2020). Although it is a generally effective treatment, not only does it completely alter the lifestyle of T1D patients who have to constantly monitor their blood sugar and inject themselves with insulin, but it is becoming rapidly more expensive in the United States. The main reason for the high cost of insulin is due to the presence of a vulnerable population that needs insulin to survive. This population, which numbers in the millions, is willing to pay any amount to receive this life-saving drug. Pharmacy companies take advantage of this fact, and price insulin at a higher price than other drugs so that they can make a significant profit. Other treatments include pancreas transplantation, but this is not a widespread treatment whatsoever. There are not enough pancreases for every diabetic to receive one, and even if they did, this would require them to take lifelong immunosuppressant drugs to prevent rejection of the organ, but these drugs have serious side effects of their own (American Diabetes Association, 2003). In an age of technology, not only are new treatments for T1D possible, but they are necessary.
Stem Cell Treatments for T1D
What are stem cells?
There are two main types of stem cells: embryonic stem cells and adult stem cells. Embryonic stem cells used in research today come from unused embryos that result from an in vitro fertilization procedure, which are then donated to science. These embryonic stem cells are pluripotent, meaning that they can turn into more than one type of cell. Next, there are adult stem cells which further divide into two separate types. One type comes from fully developed tissues such as the brain, skin, and bone marrow. However, they are more likely to only generate certain types of cells. For example, an adult stem cell from the liver will only make more liver cells. The second type of adult stem cell is induced pluripotent stem cells, which are adult stem cells that have been changed in a lab to be more like embryonic stem cells. This method has only been used since 2006, so there is still a significant amount of scientific research to be done on these cells.
The only type of stem cells that are used to treat disease now are hematopoietic stem cells that are derived from the adult stem cells in the bone marrow. However, these cells are hard to grow in a lab and are not found in large amounts in the body. Scientists are doing more research into embryonic stem cells and how they develop. A challenge with embryonic stem cells at the moment is that they are rejected by the body, so immunosuppressant drugs must be taken (Stanford Children’s Hospital, n.d.). If the embryonic stem cells are taken from the amniotic fluid when the child is still in the womb, however, the cells would match the baby genetically, and would therefore not be rejected by the immune system, so this stem cell harvesting procedure is becoming more common (Boston Children’s Hospital, n.d.)
Preliminary Research Shows Promising Results
A clinical trial conducted in Brazil compromising of 21 adults with T1D shows that stem cell infusion may help cure the disease, at least for a number of years. Results showed that most patients became insulin free for three and a half years and one patient was even free for eight years. Some stem cell transplants had little to no effect on existing T1D. The cells used in this study were autologous hematopoietic stem cells, the same type of cells found in umbilical cord blood. Harvesting blood from the umbilical cord and storing it for future use if necessary may be a good option for those, especially with a genetic predisposition to developing a medical condition, because the cells are naive and lack mutations caused by aging (CryoCell, n.d.). Researchers at the University of Florida have said that they have found a way to preserve certain cord blood cells called Treg (short for thymic regulatory) Cells which are a type of T-cell that prevent autoimmune responses, such as T1D (CryoCell, n.d.).
Making Beta Cells
Scientists at Harvard University are currently investigating how to create healthy, insulin-producing beta cells to help treat T1D patients whose beta cells are damaged. They have approached this task in four different ways: growing cells, direct differentiation, reprogramming, and self-regulation.
Researchers have refined the process of making general pancreatic endocrine cells from embryonic stem cells in the lab. Using a unique bioreactor, it is possible to grow cells at a large enough scale and at a fast enough rate to conduct experiments efficiently and extensively. After this step, scientists work on turning the general pancreatic cells into specific beta cells. This final step has been successful in live mice, but not yet in the lab setting. Once this process can be controlled, it will ensure that T1D patients can receive the right number of functioning, insulin-producing beta cells (Harvard Stem Cell Institute, 2019).
A second approach is to turn other types of pancreatic cells into beta cells, which is something that the Harvard Stem Cell Institute Director Douglas Melton, PhD has been working on. He found that this could be done by turning pancreatic acinar (digestive) cells in the live mouse into insulin-producing beta cells. This lab used a virus to make genetic modifications to these cells. This cannot be done safely in humans, but these experiments are conceptually feasible. Now, these scientists are working on the same strategy with closely related cells, such as liver cells (Harvard Stem Cell Institute, 2019).
A third approach is to take cells from patients who have diabetes and use reprogramming methods to create induced pluripotent stem cells (iPS cells), and then differentiate them into stem cells using the methods in the previous section. Dr. Melton’s lab has already created several iPS cell lines from diabetic patients with many different genetic backgrounds, but the final step is not ready to be performed in humans (Harvard Stem Cell Institute, 2019).
A fourth approach is not to turn other cells into beta cells but to get beta cells to make more of themselves. Dr. Melton’s lab has found that beta cells in the pancreas do replicate, but just at very slow rates that decrease with age. But, they have also found that these beta cells replicate much faster in pregnant mammals, due to certain genes that turn on and off during pregnancy. They are now working with several other biotechnology and pharmaceutical companies to develop drugs that could affect this pathway and stimulate beta cell reproduction (Harvard Stem Cell Institute, 2019).
Although none of the stem cell treatments mentioned above are quite ready to be used in humans, all of this scientific work shows promising results for the future. If stem cells can be used to treat T1D, the quality of life of hundreds of thousands of young and adult Americans would be significantly improved. And, the high demand for injectable insulin would decrease so large pharmaceutical companies could not force diabetics to pay such expensive prices for this life-saving drug. There is still a lot of research to be done on stem cell treatments, but it definitely is the way of the future.