In this blog post, we will look at how stem cell therapy can overcome the immune rejection response and the limitations of pancreatic transplantation in type 1 diabetes.
Of the 4-5% of the world’s population who have diabetes, about 3% have type 1 diabetes, commonly referred to as childhood diabetes. Type 1 diabetes is known to be caused by the pancreas being damaged by the immune system’s attack or by the pancreas not producing any insulin at all. Diabetes is not only a problem in itself, but it is also very dangerous because it can cause various complications in each part of the body, and it is impossible to cure it with the current level of medicine. Type 1 diabetes cannot be treated with oral medication like type 2 diabetes, so patients must rely on injection therapy to inject insulin directly into the body. However, it is very difficult for infants or adolescents to inject themselves every day, and since it only temporarily prevents the worsening of the disease, rather than being a fundamental treatment for the disease, the body can worsen further if not managed consistently in the long term.
For this reason, pancreas transplantation can be an alternative. However, when a person’s pancreas is transplanted from another person, the patient’s white blood cells may recognize the transplanted pancreas as an external substance and attack it, and the pancreas may be damaged again if the patient does not take immunosuppressants. In addition, the absolute shortage of donor pancreas is also a serious problem.
One of the ongoing research projects to address these issues is the development of treatments using stem cells. Stem cells are the basic cells that create all the cells and tissues in the body, and they are being evaluated as a potential way to address 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, which secrete insulin, in the pancreas. Therefore, research is being conducted on using 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 collected from the bone marrow and umbilical cord blood of adults and are known to exist in the body in about one million cells. Mesenchymal stem cells can proliferate indefinitely and differentiate into various cells, including fat cells, bone cells, and cartilage cells. In particular, they also have the ability to restore immune imbalances that cause the destruction of beta cells.
Therefore, if these mesenchymal stem cells are continuously cultured in a specific environment, it is possible to create cells that produce insulin. In fact, it has been proven that the ability to control blood sugar was restored after diabetes was artificially induced in an animal model using streptozocin (STZ) and then intravenous administration of mesenchymal stem cells was repeated for six months. In addition, a histology examination six months later confirmed that the mesenchymal stem cells had specifically engrafted in the liver tissue. The conclusion was that intravenous administration of mesenchymal stem cells is safe and effective in stabilizing blood sugar levels through engraftment in the liver and differentiation into insulin-producing cells.
Another method is to use embryonic stem cells. Embryonic stem cells are different from adult stem cells, which are extracted from organs or cells of adults. Embryos are in the stage of cell mass before forming organs, and reach the blastocyst stage 4-6 days after fertilization. Embryonic stem cells are cultured by separating the cell mass that forms inside the embryo. They can proliferate indefinitely and have the ability to differentiate into any cell (pluripotency). This characteristic makes them a viable source of cells to address the shortage of beta cells.
Since the pancreas is derived from endoderm, promoting its differentiation into endoderm during the early stages of development makes the differentiation into pancreatic cells more efficient. This is made possible through transcription factors. In fact, a study was conducted using embryonic stem cells from mice to induce differentiation into beta cells by introducing a gene whose expression is regulated by the insulin II promoter. In this process, differentiated cells expressed markers of pancreatic cells, including glucagon, somatostatin, pancreatic polypeptide, p48, amylase, and carboxypeptidase A, proving that differentiation was successful.
As such, these two methods have been proven effective from a technical standpoint. However, there are still issues that need to be addressed in order to implement stem cell therapy in clinical practice. First, there is a lack of an optimal protocol for inducing differentiation, which makes it difficult to use cell therapy in clinical practice. A deeper understanding of the characteristics of embryonic stem cells and the factors and specific differentiation mechanisms required for differentiation into pancreatic cells is needed. In addition, the problem of teratomas (tumors) that may arise due to the infinite proliferation of stem cells must be addressed. Since stem cells themselves have the property of infinitely proliferating, there is a possibility that they will grow into teratomas.
One of the biggest social issues with stem cell technology is the ethical question. If one’s own somatic cells are placed in a denucleated egg and cultured, the embryo will reach the blastocyst stage and become an embryonic stem cell. Using one’s own somatic cells at this stage can be considered a form of cloning, which raises ethical and dignity issues related to human cloning.
Although there are still many challenges to be solved, if these problems can be overcome, stem cell technology will be a great hope for the many children with diabetes who rely on insulin injections every day.
