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Stem Cell Treatments – Type 1 Diabetes
Type 1 diabetes is an autoimmune disease of the pancreas. In healthy people, the insulin-producing beta cells – located on the islets of Langerhans in the pancreas – are damaged by the autoimmune attack. This leads to a reduction of the pancreas’s ability to produce insulin. Insulin is required to maintain a stable level of glucose in the blood. When the pancreatic beta cell mass is damaged to the point that it can no longer produce enough insulin to maintain glucose homeostasis (usually when 60 to 80% is destroyed), the patient is clinically diagnosed.

There are currently no consistently successful stem cell treatments for type 1 diabetes, though several are being developed. The focus of such treatments is on regenerating or preserving the damaged beta cell mass. However, beta cells do not have their own stem cells. Therefore, other sources of stem cells are being investigated. There are currently two different approaches: the use of adult stem cells, and the use of embryonic stem cells.

Adult Stem Cells

The most common source of adult stem cells is the reserve of hematopoietic stem cells in bone marrow. These cells could be used to regrow beta cells in newly diagnosed patients (who may still retain a small mass of functional beta cells, and therefore, insulin production). Ideally this would create stem cells and regenerated beta cells that are genetically part of the patient, reducing the risk of graft-versus-host immune attack that is the cause of the disease in the first place.

In November of 2003, a the first study was done using stem cell therapy to treat type 1 diabetes in humans. This study, conducted in Ribeirão Preto, Brazil, included 15 patients of both genders between the ages of 14 and 35, all of whom had been diagnosed within the past 6 weeks. The patients were given high dose immunosuppression to prevent graft-versus-host complications. Following that, they were given cyclophosphamide and granulocyte colony-stimulating factor to mobilize the stem cell colonies. After they were harvested, the blood stem cells were conditioned with cyclophosphamide and antithymocyte globulin. The cells were then infused back into the patients, who were then given more granulocyte colony-stimulating factor until neutrophil count was greater than 1000/µL.

The results of this study were promising. Only one of the patients failed to receive any clinical benefit, which was thought to be a result of a significantly lower beta cell reserve at the beginning of the study, indicated by an episode of diabetic ketoacidosis. Of the other 14 patients, 13 were insulin-independent by February of 2007. This period of remission lasted from 1 to 35 months, with a mean of 16.2.

Embryonic Stem Cells

Embryonic stem cells have also been used in an attempt to grow new beta cells that could be implanted into the patient. This could be particularly helpful in patients who have been insulin-dependent for an extended length of time – meaning their beta cell mass is almost completely destroyed and they have lost the ability to produce any insulin at all. However, this approach has been full of dead ends.

The most promising study so far was conducted by Emmanuel Baetge of Novocell. Baetge used an embryonic stem cell line to mimic the developmental stages of pancreatic tissue, starting with endoderm. The team was then able to create cells that would then bud into a pancreas. These were committed to their pancreatic destiny, but did not produce insulin. The researchers figured out what growth factors were necessary, allowing the cells to produce insulin and other regulatory hormones, but they would not respond to glucose levels. Although this was a significant problem, the team implanted these cells into diabetic mice – with no result. They then took a step back, and implanted into 24 diabetic mice the cells that were committed to becoming a pancreas, but didn’t produce insulin. The idea was that the in vivo environment would guide the cells’ development into a functional beta cell. The graft failed in two of the mice, but the other 22 were cured. This study has yet to be conducted on humans, but the result is promising.