Type 1 Diabetes is a disease that affects hundreds of thousands of people every day. It is an autoimmune disorder in which the pancreas does not produce any insulin or glucagon. Due to this lack of hormones, the patient must take shots daily in order to survive. It "is a life sentence to a difficult therapeutic regimen that is only partially effective in preventing acute and chronic complications" (Devendra et al. 750). This can cause many complications throughout the patient's lifetime such as "retinopathy, neuropathy, and nephropathy, as well as cerebrovascular and cardiovascular disease" (Godfrey et al. 14). As someone who has been living with Type 1 Diabetes for over two years, I can attest to the struggles and complications that come along with this disease. There have been several mornings where I have woken up and wondered if I will make it through the day due to hyperglycemia, a serious side effect of diabetes. Hyperglycemia is a term used to describe high blood glucose. It affects every organ in the body, and can lead to diabetic ketoacidosis. This is when your body isn't breaking down any glucose due to a lack of insulin, which turns your blood acidic. If left untreated, this will lead to a coma, and eventually death. Another common side effect of Type 1 Diabetes is hypoglycemia, which is the term used to describe low blood sugar. Hypoglycemia can cause seizures and potentially brain damage if left untreated. Diabetes is a twenty-four hour job that your life depends on, and if not taken seriously, can result in serious complications. I have been hospitalized three times due to this disease, and it is a very scary and unpredictable thing to have to live with. Thankfully, there are many options being explored to treat and/or cure this disease. One of the most promising methods being studied is stem cell therapy because of its "unique capability to produce undifferentiated daughter cells or generate specialized cell types" (Godfrey et al. 14), and its "intrinsic regenerative capacity and immunomodulatory potential" (Chhabra et al. 2). These characteristics are what make stem cells ideal for not only curing diabetes, but also in treating symptoms that are caused by diabetes. However, there are many downsides associated with using these treatments, and controversy has arisen over the issue of whether the benefits outweigh the costs of using these treatments. 

One of the most common side effects caused by diabetes are diabetic foot ulcers. Heublein, Bader, and Giri stated that "diabetic foot ulcers (DFUs) occur in 15% of all patients with diabetes," which includes patients with both Type 1 and Type 2 Diabetes (703). Diabetic foot ulcers cause "84% of all lower leg amputations" (703). This is a significant amount of amputations and stem cell therapy could help drastically lower this number. Fibroblasts are a common type of cell currently being studied for regenerative therapy for wounds in diabetics. In a clinical study evaluating the rate of wound healing, those infused with fibroblasts had a faster rate of wound healing due to its "production of growth factors and ECM [extracellular matrix] protein[s] as well as the promotion of angiogenesis" (Khamaisi et al. 847). Fibroblasts promote the growth rate of new blood vessels, which in turn speeds up the healing process of diabetic wounds. However, fibroblasts have been found to "induc[e] insulin resistance in diabetic patients" (848). This can be detrimental because diabetics rely on insulin in order to live, and an increase in insulin resistance would cause hyperglycemia, furthering the diabetic patient's problems. While there are other stem cells being researched, such as bone marrow-derived mesenchymal stem cells, bone marrow-derived mononuclear stem cells, peripheral blood mononuclear cells, placenta-derived stem cells, umbilical cord blood-derived stem cells, adipose tissue-derived stem cells, and human fetal aorta-derived progenitor cells, these also have many side effects associated with them. For instance, inflammation, reduced endothelial repair, and retinopathy have all been associated with the use of these different stem cells. Although not proven, oncogenic risks are also a major concern with stem cells because they could cause the patient to develop tumors. Despite fostering more medical conditions, money is one of the biggest factors concerning stem cell therapy. "In the USA alone, the annual costs of diabetes-related amputations and diabetic wound treatment are approximately $3 billion and $9 billion, respectively" (Heublein et al. 714-715). This imposes a major economic impact both on the health industry and on the patients themselves. Nonetheless, there is likely to be a safer, and more cost-effective treatment in the near future. 

Since Type 1 Diabetes begins with the destruction of beta cells in the pancreas, it seems most reasonable that pancreatic stem cells would be the most beneficial place to obtain stem cells from. Currently, beta cells located in the Islet of Langerhans are the only cells capable of sensing the body's blood glucose and utilizing that to secrete the proper amount of insulin (Rother, Harlan 877). Unfortunately, beta cell transplantation is a relatively short-lived process. After a while, the body begins to attack the new beta cells, taking the patient back to square one. In order to combat this reaction, the patient is prescribed immunosuppressants, which prevent their body from attacking the new beta cells. Even with this medication, "few patients remain insulin independent beyond four years after transplantation" (877). This short duration makes one wonder if the pros of this treatment outweigh the cons. In a clinical study, six females underwent islet cell transplantation and were put on immunosuppressants to prevent their bodies from rejecting the new cells. Half of the patients were insulin independent after one year, but the other half had to discontinue the immunosuppressant therapy because of the side effects (Hirshberg et al. 3288). Some would say it isn't worth it due to the complications, including possible second transplantation, mild hyperglycemia, fatigue, diarrhea, weight loss, decreased kidney function, partial portal vein thrombosis, intra-abdominal hemorrhage, and sirolimus-induced pneumonitis (3288-3291). However, as a Type 1 Diabetic I would be willing to participate in as many clinical trials as it took to finally develop a cure. 

 A potential solution to having to use immunosuppressants is microencapsulating the islet transplantation cells. This would "prevent physical, cell-to-cell contact between the host and the transplanted cell/tissue, thereby virtually circumventing the islet graft-directed immune destruction" (Stem Cells for ...  1). Providing a barrier that would prohibit the body from attacking the islet cells would eliminate the need for multiple islet transplantations, as well as the need for immunosuppressants. This would make the transplantation process much more effective, and safer for the patient. In the University of Perugia Experience, four patients undertook encapsulated islet transplantation. The goal of this study was to determine the long-term effect of using microencapsulated islet cells. The only adverse effects reported was from one patient who had abdominal discomfort due to a cyst-like mass (Clinical Application of ...  88). Most would agree the overall benefits of this procedure outweigh the minor surgery required to remove the mass from the patient's body. According to Calafiore, Riccardo and Basta, the most important finding was that the "microcapsules prevented any detection of foreign antigens by the host, despite the lack of immunosuppressive treatment" (88). This is extremely important because it verifies that the microencapsulation of islet cells does in fact prevent them from being rejected by the body. This could also potentially allow for the grafting of islet cells across different species. Despite this possibly profound breakthrough, the issue of quantity is still a factor. Obtaining the masses of islet cells needed to perform this treatment is still a barrier that must be overcome, but this trial has led us one step closer to developing a cure.  

Embryonic stem cells are one of the most popular stem cells used in the medical field. They have the "highest differentiation potential into insulin-secreting cells" (Stem Cells for ...  24). This differentiation causes the cells to be able to secrete insulin, which will in turn reverse the hyperglycemia. The downside of this is that the embryonic stem cells were not able to secrete insulin solely in response to high blood glucose levels (25). If insulin is secreted when blood glucose levels are low, this will lower the blood glucose level even farther, causing hypoglycemia, which could in turn cause the patient to pass out and seize. In Godfrey, Matthew, Bulman, Shah, Clement, and Gallicano's study, they were also not able to manipulate the embryonic stem cells to produce insulin. Yet, they discovered that "human embryonic stem cells will respond to environmental signals to bring about islet-cell formation" and that there is a correlation between mouse and human cells, which could be useful in transplantation across the species" (20). The rapid replication embryonic stem cells undergo is beneficial in producing multitudes of islet cells, but this increases the probability that the embryonic stem cells turn tumorigenic. These risks could be decreased by "increasing differentiation status and commitment to the cell type before transplantation in patients", but it can still contribute to "oncological risk" (Stem Cells for ...  25). However, this is a risk that cannot be avoided when rapid cell division is needed. There is a lot of controversy surrounding embryonic stem cells due to their origin. Yet this could give them the benefit of having a potentially endless supply, which is one of the most difficult setbacks associated with stem cells. 

Mesenchymal Stromal Cells [MSCs] are one of the more diverse types of stem cells due to their location in many different places in the body. They have also been found to be helpful in treating a multitude of other diseases. Carlsson, Korsgren, and Le Blanc stated that, "MSCs are perhaps one of the most interesting candidates for use in the treatment of type 1 diabetes based on their anti-inflammatory and immunomodulatory capacities" (5). MSCs are said to have positive effects on tissue repair, inflammation, and immunity, which would be very beneficial for use in Type 1 Diabetics. The most common form is found in bone marrow, but they can also be found in most tissues including the heart, endometrium, adipose tissue, placentas, and dental pulp (2). One of the most dangerous complications with diabetes is hyperglycemia. It has been proven that "MSCs have improved metabolic control and even reversed the hyperglycemia" in experimental studies (4). This reversal of hyperglycemia is the most crucial element in curing Type 1 Diabetes.  MSCs are also beneficial in promoting tissue repair, which aids in the healing of wounds that are common to diabetics, as previously mentioned. Surprisingly, "no or only minor side effects of treatment have been observed in these or other clinical studies. No increased risk of tumor development in patients is known, and no ectopic tissue formation has been observed" (3). Unlike many other stem cells, there are not any side effects that are associated with these cells that have been reported. However, they do share the common drawback that the clinical trials do not encompass a large clinical group. MSCs were also clinically tested in the treatment of Type 1 Diabetes. It was determined that they were beneficial in treating diabetes for at least a year. However, "larger blinded studies [] with a longer duration of follow-up after MSC treatment are needed to verify these initial promising results" (6). A larger trial group would allow for more variation, and would give a more accurate representation of how beneficial the MSCs are. Also, a longer trial duration would provide better insight into the potential side effects associated with these cells over time. 

Stem cell therapy is currently the most researched method that could be used to cure Type 1 Diabetes. There is an abundance of research on stem cells, yet the quantity of clinical trials are still lacking. Diabetics everywhere are anxious for the day when they might get the opportunity of a lifetime to participate in one of these clinical trials. While there may be some setbacks and side effects from the use of stem cells, finding a cure will trump all of the negatives. Stem cells show great promise for the future, and will just continue to improve over time. However, "despite improvements in care, the disease still takes a terrible toll on quality of life" (Rother and Harlan 881). As someone extremely familiar with this disease, I can corroborate to the uphill battle that diabetes is and how it can seem like an endless life of needles and worry and anxiety. Yet, there is thankfulness in my heart for the maturity, responsibility, and appreciativeness that this disability has given to me. This has made me an advocate for using stem cell therapy to continue the search for a cure to Type 1 Diabetes. 

