Remarkable research pointing to a potential new treatment for diabetes was announced this week at Georgetown University Medical Center in Washington, D.C. Scientists succeeded in transforming spermatogonal stem cells, early precursors of sperm cells, into insulin-secreting cells. It is likely that the work represents significant progress in accomplishing the Holy Grail of diabetes research, the replacement of insulin-secreting cells lost to the disease.
In type I diabetes, the early onset form of the disease that often occurs in young children, cells of the pancreas called islet cells or beta cells, which normally secrete insulin, are lost due to autoimmunity. The body’s own immune system attacks and destroys these cells, leaving the sufferer insulin-deficient. Since insulin controls and amplifies the pumping process that transports glucose (sugar) from the blood into the body’s cells to supply fuel, high levels of blood glucose result, and cells are starved of energy. The condition is potentially lethal and must be treated with injections of insulin.
In type II diabetes, which has a later onset, the sufferers retain their islet cells, but the cells do not make enough insulin, probably as the result of genetic vulnerabilities to the disease, which may be exacerbated by excess food consumption and lack of exercise. In the most severe forms of this type of diabetes, the patients also need insulin injections.
The Georgetown scientists obtained new insulin secreting cells by removing about a million of these cells (1 gram) from the testes of deceased human organ donors. They then transplanted the human cells to the backs of diabetic mice that were also deficient in immunity, so that the animals did not reject the human cells. The researchers did nothing more with the cells. In a short time, some of the testis-derived stem cells transformed themselves into cells secreting insulin, which then lowered the levels of glucose in the mice’s blood. The human cells remained active in the mice for about a week.
One of the most remarkable aspects of the research is that no additional genes were added to the testis stem cells. As pluripotent stem cells, they already possessed the latent capacity to secrete insulin. The lead investigator and director of the Transgenic Core Facility at GUMC, G. Ian Gallicano, said, “We found that once you take these cells out of the testes niche, they get confused, and will form all three germ layers within several weeks. These are true, pluripotent stem cells.”
In the past to treat diabetes, insulin-secreting islet cells have been transplanted from organ donors into patients. And insulin-secreting cells have been produced from other kinds of adult cells by the addition of genes or transcription factors to reprogram the cells or restore them to the stem-cell state. But both procedures have drawbacks. Islet cell transplantation must be followed by immunosuppression, which can be associated with severe adverse effects, in order to prevent transplant rejection. Adult stem cell reprogramming to treat diabetes, which remains an experimental procedure at present, can give rise to tumors.
In contrast, one can envision the possibility of a better source of new insulin-secreting cells for diabetics, if the Georgetown researchers make progress with their spermatogonal cell technique to the point that it may be used to treat humans. Male sufferers of the disease, at least, might undergo transplantation of stem cells from their own testes to other regions of their own bodies, in order to produce new insulin-secreting cells. Such a treatment would avoid the drawbacks of immunosuppression, since the cells would not trigger rejection. And risks of inducing neoplasms might be avoided.
In recognizing this remarkable work, one might take note of the fact that Georgetown University is a Jesuit institution. Theologically opposed to stem cell research with human embryos, the scientists at the medical center may have concentrated on working with stem cells from the tissues of adults. Thus, it may result that their religious outlook could lead to a wonderful advancement in the treatment of diabetes.