Title: The Era of Designer Cell Engineering
Author: Andrea Friedlander
Category: UNSW Research


Insulin use to treat diabetes has long been established. Could there be a new treatment for diabetics?

Blood sugar is converted to energy by a hormone called insulin, which is produced by a cell in the human pancreas called a ß-cell. Type 1 diabetes is said to occur where ß-cells are not present or not functioning to perform this task. Current therapy for type 1 diabetes involves giving the body “shots” of insulin, usually by injection. These methods replace the insulin that is absent in a diabetic but it does not mimic the natural methods which the body naturally introduces in a healthy individual. Fluctuations of blood glucose levels from the artificial insulin can cause long term complications such as damage to your eyes, kidneys, and peripheral nerves.

ß -cells produce insulin on a minute-by-minute basis, consistent with the body's needs. When glucose levels are high insulin acts to transport glucose into the cell. This microscopic type of regulation cannot be as finely controlled with two or three daily injections of insulin. Rather than supplementing the body with artificial insulin, there are new horizons in achieving the body's natural way of modulating insulin for people with type 1 diabetes.

Analogous to an organ transplant, there are new therapies being developed which involves the transplantation of healthy insulin-producing cells to replace the Type 1 diabetics' ß-cells that do not produce insulin. The transplanted ß-cells cells would regulate glucose levels much as the body does in people without diabetes, by responding to the body's constantly changing requirements.

Recently, human trials have commenced elsewhere with ß-cells isolated from the pancreas of human donors. One of the shortcomings of this technique is a non-scientific concern. There is a shortage of donors, with 206 Australians donating organs in 2002 and 100,000 people in this country with type 1 diabetes.

The Diabetes Transplant Unit (DTU), under the direction of Professor Bernie Tuch at the Prince of Wales Hospital is concentrating on a number of methods to generate healthy ß-cells that can be transplanted into diabetes patients. Researchers at the DTU were the first group in the world to successfully normalize blood glucose levels of diabetic pigs transplanted with immature pig ß-cells. Currently, transplantation of these cells is being carried out into monkeys in pre-clinical trials. Draft guidelines for transplanting such cells into humans have recently been developed by the National Health and Medical Research Council of Australia. Not surprisingly Professor Tuch indicated that it was only a matter of time before the guidelines were finalized and ratified, and applications for human trials with pig ß-cells could be submitted for consideration.

Further exciting possibilities in the creation of healthy ß cells are from the use of stem cells that have yet to specialise and be committed to a tissue or organ. This property has been the focus of scientific research as it opens up the possibility for the growth of desired tissue or organs, including pancreatic ß-cells, which can be transplanted into patients (Stocum 2002; Stanworth and Newland 2002).

Stem cells under the microscope Image : East Carolina University

Stem cells can be found in 3-5 day embryo's and in the bone marrow of adults. The use of adult stem cells (AS) has the advantage in that they could be taken from the patient, cultured, and reintroduced, AS cells are also less ethically problematic in the political arena compared to the use of embryonic stem cells, which are harvested from embryonic tissue, such as excess embryos from in vitro fertilization efforts. However, in the DTU lab, embryonic stem cells (ES) are more readily converted into ß cells despite the fact that researchers there have been experimenting for a longer time on the AS cells.

In December 2002 federal legislation was passed permitting scientists not only to work with existing ES cell lines but also to create new lines from surplus in vitro fertilization embryos. Researchers in the DTU have been successful in converting mouse ES cells into ß cells, and they are attempting the same outcome with human ES cells. With the achievements of the DTU thus far, and the support of Australian parliamentarians in backing regulated, embryonic stem cell research, it is clear that this team of scientists will impact and facilitate the quest to create new ß cells, perhaps progressing toward freeing diabetics from their daily injections.

References

Bliss, M. 1988 The discovery of insulin, Faber and Faber, London Boston

Online NHMRC; http://www.nhmrc.gov.au/issues/xeno.htm

Stocum, D.L. 2001 Stem cells in regenerative biology and medicine. Wound Repair & Regeneration. 9(6), 429-42

Stanworth, S.J. and Newland A.C. Stem cells: progress in research and edging towards the clinical setting. Clinical Medicine. 1(5), 378-82

Glossary

Adult stem cells:
Undifferentiated cells found among differentiated cells in a tissue or organ. These cells can renew themselves, and can differentiate to yield major specialised cell types of the tissue or organ. For example, adult tissues such as the bone marrow and brain have discrete populations of adult stem cells that can generate replacements for cells that are lost through injury or disease. The origin of adult stem cells in mature tissues is unknown. Adult stem cells cannot be proliferated in the long term in the laboratory without differentiating.

ß (beta) cells:
Insulin producing cells of the pancreas.

Embryonic stem cells:
Puripotent cells derived from the inner cell mass of a 3-5 day old embryo. Embryonic stem cells can generate many cell types of the body derived from all three embryonic cell types: endoderm, mesoderm and ectoderm. These cells can be proliferated for a year or more in the laboratory without differentiating.

Stem cells:
Unspecialised cells that renew themselves for long periods through cell division. They can be induced to become cells with special functions, such as the insulin-producing cells of the pancreas.