Type 1 diabetes is caused by damage to insulin-secreting cells, and conventional treatments do not offer a cure. Stem cell therapy offers the promise of replacing beta cells and addressing immune rejection and the lack of donor pancreases, but technical and ethical challenges remain for clinical application.
Approximately 3% of people with diabetes, which accounts for 4-5% of the world’s population, have type 1 diabetes, commonly referred to as juvenile diabetes. Type 1 diabetes is believed to be caused by a congenital inability to produce insulin at all, or by damage to the pancreas due to immune cell attack. Diabetes is not only a problem in itself, but it is also very dangerous as it can lead to a variety of complications in different parts of the body, and it is impossible to cure with the current state of medical science. In particular, type 1 diabetes cannot be treated with oral medication like type 2 diabetes, so we have to rely on injection therapy, which involves injecting insulin directly into the body. However, it is very difficult for a child or teenager to give themselves injections every day, and since it is not a cure for the disease, but only temporarily stops the disease from getting worse, the body can get worse if it is not managed consistently in the long run.
For this reason, pancreas transplantation is one alternative. However, when someone else’s pancreas is transplanted, the patient’s white blood cells may recognize the transplanted pancreas as foreign and attack it, and if the patient does not take immunosuppressive medication, the pancreas may be damaged again. In addition, the absolute shortage of donor pancreases is also a serious problem.
To address many of these issues, one ongoing research effort is the development of treatments using stem cells. Stem cells are the basic cells that give rise to any cell or tissue 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 insulin-secreting beta cells in the pancreas, so researchers are focusing on these beta cells and using adult stem cells, which are primitive cells just before they differentiate into cells of a specific organ. Mesenchymal stem cells, a type of adult stem cell, are harvested from the bone marrow and umbilical cord blood of adults, and there are thought to be about 1 million of them in the body. Mesenchymal stem cells can proliferate indefinitely and differentiate into a variety of cells, including adipocytes, bone cells, and chondrocytes. They also have immunomodulatory abilities, especially to repair immune imbalances that cause the destruction of beta cells.
Therefore, when these mesenchymal stem cells are continuously cultured in specialized cultures, they can produce insulin-producing cells. In fact, after artificially inducing diabetes in an animal model using streptozocin (STZ), repeated intravenous administration of mesenchymal stem cells for six months restored glycemic control. Furthermore, histologic examination six months later confirmed that mesenchymal stem cells had specifically engrafted into liver tissue. The liver engraftment and differentiation into insulin-producing cells led to the conclusion that intravenous administration of mesenchymal stem cells is safe and effective in stabilizing blood glucose.
Another approach is to use embryonic stem cells. Embryonic stem cells are different from adult stem cells, which are derived from adult organs or cells. An embryo is a clump of cells before it forms organs, and four to six days after fertilization, it reaches the blastocyst stage. At this point, the clump of cells inside the embryo is isolated and cultured into embryonic stem cells. Embryonic stem cells can multiply indefinitely and have the ability to differentiate into any cell (pluripotency). This property allows them to serve as a source of cells to address the shortage of beta cells.
Since the pancreas arises from a full endoderm, promoting full endoderm differentiation during early development makes differentiation into pancreatic cells efficient. This is accomplished through transcriptional regulators. In fact, there was a study that used mouse embryonic stem cells to differentiate into beta cells by introducing a gene whose expression of β-geo is regulated by the insulin II promoter, and the differentiated cells expressed markers of pancreatic cells such as glucagon, somatostatin, pancreatic polypeptide, p48, amylase, and carboxypeptidase A, which proved that the differentiation was successful.
While these two methods have proven effective from a technical standpoint, there are still issues that need to be addressed before stem cell therapies can be implemented in the clinic. First, the optimal protocol for inducing differentiation has not been established, making it difficult to utilize cell therapy in the clinic. A deeper understanding of the properties of embryonic stem cells and the factors and specific differentiation mechanisms required for their differentiation into pancreatic cells is needed. We also need to address the issue of teratomas (tumors), which can arise due to the infinitely proliferative nature of stem cells themselves, and the potential for them to grow into teratomas.
One of the biggest societal issues with stem cell technology is ethical. When an unfertilized egg is cultured with your own somatic cells, it reaches blastocyst stage and becomes an embryonic stem cell. The use of one’s own cells can be considered a form of cloning, raising the ethical controversy and dignity issues of human cloning.
There are still many challenges to overcome, but if these can be overcome, stem cell technology could offer great hope to the millions of pediatric diabetics who rely on daily insulin injections.
