Stem cells are seen as the miracle cure of the future for many degenerative diseases. Scientists and physicians also hope that stem cells will exert their regenerative effect in the treatment of diabetes type 1 which is caused by damaged tissue. Prof. Dr. Jochen Seufert and Dr. Günter Päth from the University Hospital of Freiburg are investigating whether it is possible to use certain types of stem cells to regenerate the body’s own insulin production. The biological relationships involved have proved to be very complex. The two specialists are quick to point out that an early cure is not likely. However, they are cautiously optimistic about the far-reaching potential of stem cells.
Diabetes type 1 is an autoimmune disease. In diabetes patients, the body’s defence system has an allergic reaction to the ß-cells in the pancreas. The immune cells attack and destroy the ß-cells. The body is no longer able to produce insulin, which is needed to break down sugar. Diabetes sufferers depend on artificial insulin that they normally have to inject. Although this type of therapy saves many lives, it is nevertheless not an optimal solution as insulin is unable to precisely regulate the blood sugar level. This often leads to blood sugar values that are too high or too low, which in turn drastically reduces sufferers’ quality of life and also leads to diabetic complications later on. “The transplantation of insulin-producing cells might offer a better possibility of treating the disease,” said Prof. Dr. Jochen Seufert, head of Endocrinology and Diabetology in the Department of Internal Medicine II at the University Medical Centre Freiburg. “But this type of treatment also has its disadvantages.”
Nowadays, physicians either transplant a whole pancreas or just the part that contains the ß-cells, i.e. the islet of Langerhans. With such cell therapy methods, it is always necessary to suppress the immune system of the recipient with immunosuppressive drugs in order to prevent the foreign cells from being rejected. In terms of the side effects, it is generally only patients who have received a new kidney due to serious diabetic complications, and whose immune system needs to be suppressed anyway that receive this kind of treatment. The transplantation of the entire pancreas is a difficult and complicated intervention. If the organ is not rejected, sufferers who received treatment can live for many years without having to use insulin injections. The second method, i.e. the transplantation of islets of Langerhans, is a minor intervention requiring only the puncturing of the portal vein and the introduction of the islets of Langerhans. This can be done on an outpatient basis. However, the success rates for this procedure are a lot lower. After two years, only 20 percent of those treated still remain independent from artificial insulin. The residual function of the islet transplant persists, even when sufferers have to start injecting insulin again to prevent dangerous hypoglycaemia. Both options have their limitations: there are far too few donor organs compared to the large number of people waiting for a transplant. "Therefore, researchers are working hard to find an alternative source of ß-cells and grow them from stem cells in the reaction tube," said Seufert. "The basic idea is to exploit the regenerative potential of stem cells."
Stem cells from embryonic tissues, but also many stem cell types taken from the tissue of adults, can differentiate into different cell types. Will it one day be possible to convert these stem cells into ß-cells in the test tube and transplant them into the pancreas of sick patients? “Initial results with human, mouse and rat cells provide evidence that this is in principle possible,” said Dr. Günter Päth, head of laboratory in Seufert’s department. However, there are some problems associated with this plan: the ß-cells can only be proliferated in the test tube with difficulty, they do not produce sufficient insulin and they do not release sufficient quantities of insulin when the sugar level rises. In the case of embryonic stem cells, the transplantation of new ß-cell tissue can also cause cancer. If the transplanted cell mass contains some non-differentiated stem cells, they can resume division, growing in an uncontrolled way to form tumours.
Seufert, Päth and their teams are concentrating on adult stem cells, in particular on mesenchymal bone marrow stem cells. "This bone marrow stem cell type seems to act like a kind of repair police, because it is found in damaged organs," said Seufert. " The stem cells themselves do most likely not differentiate into the cell types required at the site of injury or damage. But they induce other cells to undergo cell division thus contributing to regeneration." The scientists are currently investigating whether the repair police are also able to stimulate transplanted ß-cells of the pancreas to regenerate. This might contribute to the survival of the transplant and prolong the time a patient can live without having to inject insulin. "If this turns out to be the case, then we will start to look for the molecular mechanisms behind this," said Päth explaining that it is necessary to understand the mechanisms in detail before new types of therapy can be developed. One day it might be possible to exploit the helper function of mesenchymal stem cells and, in combination with a drug cocktail, induce ß-cells of diabetics to divide.
However, Seufert and Päth consider it to be irresponsible to announce publicly that it is possible to use mesenchymal stem cells for the treatment of diabetics before comprehensive scientific studies have been carried out. Their opinion is backed by the German Diabetes Society (DDG). The “Diabetes Mellitus Competence Network”, funded by the German Federal Ministry of Education and Research, was started in 2008 as a platform for systematic investigations. Researchers from Freiburg are working with 23 groups from all areas of experimental and clinical diabetology in the development of new therapies and the improvement of existing ones. “We still know far too little about the complex molecular relationships of stem cell biology,” said Päth. How can stem cells be directly programmed? In this case, it is not only the genetic information that plays a decisive role. It is becoming more and more obvious that epigenetic mechanisms play a decisive role in the way genetic information is read in the cell. Päth compares the human body to a computer with an operating system that has all possible programmes and errors. “We have very little knowledge about the programming language which we could use to manipulate the functions in such a computer,” said Päth. “It will take another ten or twenty years to decipher the functions.” Nevertheless, both Seufert and Päth believe in the huge potential of stem cells. “Of course, stem cells cannot help us combat the cause of diabetes mellitus type 1, i.e. the disorder in the immune system,” said Seufert. “But I envisage that stem cells will one day be able to alleviate the symptoms and help us avoid the disadvantages associated with insulin replacement therapies or pancreas or ß-cell transplantation.”
Further information: Prof. Dr. med. Jochen SeufertEndocrinology and DiabetologyDepartment of Internal Medicine IIUniversity Medical Centre FreiburgHugstetter Str. 5579106 Freiburg/Brsg.Tel.: +49 (0)761/270-3634Fax: +49 (0)761/270-3413E-mail: jochen.seufert(at)uniklinik-freiburg.deSecretarial Office: Ms. MartinezTel.: +49 (0)761/270-3420Fax: +49 (0)761/270-3413E-mail: clara.martinez(at)uniklinik-freiburg.de
Günter Päth, PhDLaboratory B9Endocrinology and DiabetologyDepartment of Internal Medicine IIUniversity Medical Centre FreiburgHugstetter Str. 5579106 Freiburg/Brsg.Tel.: +49 (0)761/270-7327Fax : +49 (0)761/270-3372E-mail: guenter.paeth(at)uniklinik-freiburg.de