In this blog post, we explore how stem cell therapy might overcome the immune rejection response and the limitations of pancreas transplants in type 1 diabetes.
Among the 4–5% of the global population living with diabetes, approximately 3% have Type 1 diabetes, commonly known as juvenile diabetes. Type 1 diabetes is known to occur either because the body is unable to produce insulin from birth or because the pancreas is damaged by attacks from immune cells. Diabetes is not only a problem in itself but is also extremely dangerous because it can cause various complications in different parts of the body, and a cure is not possible with current medical technology. In particular, since type 1 diabetes cannot be treated with oral medication like type 2 diabetes, patients have no choice but to rely on insulin therapy, which involves injecting insulin directly into the body. However, it is very difficult for infants or adolescents to administer injections to themselves every day. Furthermore, since this is not a cure for the disease but only serves to temporarily prevent its progression, the patient’s condition may worsen over time without consistent, long-term management.
For these reasons, a pancreas transplant can be a viable alternative. However, when a pancreas from another person is transplanted, the patient’s white blood cells may recognize the transplanted pancreas as a foreign substance and attack it; furthermore, if the patient does not take immunosuppressants, the pancreas may be damaged again. Additionally, the severe shortage of donor pancreases is a major problem.
To address these various issues, one of the ongoing research efforts is the development of treatments using stem cells. Stem cells are the fundamental cells that can generate all other cells and tissues in the body, and they are considered a potential solution to the problems of transplant rejection and the shortage of donor pancreases. First, type 1 diabetes is a disease caused by the destruction of beta cells—the pancreatic cells that secrete insulin. Therefore, research is underway to use adult stem cells, which are primitive cells just before they differentiate into specific organ cells, with a focus on these beta cells. Mesenchymal stem cells, a type of adult stem cell, are harvested from adult bone marrow and umbilical cord blood, and it is known that approximately 1 million of them exist in the body. Mesenchymal stem cells can proliferate indefinitely and differentiate into various cell types, such as fat cells, bone cells, and cartilage cells. In particular, they possess immunomodulatory capabilities that can restore the immune imbalance causing the destruction of beta cells.
Therefore, by continuously culturing these mesenchymal stem cells under specific conditions, it is possible to generate insulin-producing cells. In fact, after artificially inducing diabetes in an animal model using STZ (streptozocin), repeated intravenous administration of mesenchymal stem cells over a 6-month period demonstrated that blood glucose control was restored. Furthermore, a biopsy performed six months later confirmed that the mesenchymal stem cells had specifically engrafted in the liver tissue. Based on this liver engraftment and differentiation into insulin-producing cells, it was concluded that intravenous administration of mesenchymal stem cells is safe and effective for stabilizing blood glucose levels.
Another method involves the use of embryonic stem cells. Embryonic stem cells differ from adult stem cells, which are extracted from adult organs or cells. An embryo is a mass of cells prior to organ formation; approximately 4 to 6 days after fertilization, it reaches the blastocyst stage. Embryonic stem cells are derived from the mass of cells that forms inside the embryo at this stage, which is then isolated and cultured. Embryonic stem cells can proliferate indefinitely and possess the ability to differentiate into any type of cell (totipotency). This characteristic enables them to serve as a cell source capable of addressing beta cell deficiency.
Since the pancreas develops from the endoderm, promoting differentiation into the endoderm during early development makes the differentiation into pancreatic cells more efficient. This is made possible through transcriptional regulatory factors. In fact, there have been studies attempting to induce differentiation into beta cells by introducing genes whose expression is regulated by the insulin II promoter into mouse embryonic stem cells. During this process, the differentiated cells expressed pancreatic cell markers such as glucagon, somatostatin, pancreatic polypeptide, p48, amylase, and carboxypeptidase A, proving that differentiation was successful.
Thus, both methods have been proven effective from a technical standpoint. However, there are still issues that need to be resolved before stem cell-based therapies can be implemented clinically. First, since an optimal protocol for inducing differentiation has not been established, it is difficult to utilize this approach for cell therapy in clinical settings. A deeper understanding of the characteristics of embryonic stem cells, as well as the factors and specific mechanisms required for differentiation into pancreatic cells, is necessary. Additionally, the issue of teratomas (tumors), which can arise due to the unlimited proliferative capacity of stem cells, must be addressed. Since stem cells themselves possess the ability to proliferate indefinitely, there is a potential risk of them developing into teratomas.
One of the most significant social issues surrounding stem cell technology is the ethical dilemma. When a patient’s somatic cells are introduced into an enucleated oocyte (an egg from which the nucleus has been removed) and cultured, the resulting blastocyst produces embryonic stem cells. Using a patient’s own somatic cells in this process can be considered a form of cloning, raising ethical controversies and concerns about human dignity associated with human cloning.
Although many challenges remain to be resolved, if these issues can be overcome, stem cell technology will offer great hope to the countless children with diabetes who currently rely on daily insulin injections.
