Can stem cells ‘cure’ diabetes? Lessons from two trials

MANY APPROACHES TO RESTORE INSULIN SECRETION

For this, scientists tried out pancreatic transplant, islet cell transplant or stem cell transplant. Islet cells in the pancreas are composed of beta cells that produce insulin and alpha cells that produce glucagon. Although islet transplants can restore insulin secretion, there aren’t enough donors and they require the use of immune-suppressing drugs to prevent the body from rejecting the donor tissue.

Stem cells are a special type of cells that can differentiate into specialised cells. They have to be programmed or guided to develop into insulin- secreting pancreatic islet cells. Stem cells can be cultured in the laboratory and potentially offer an endless source of pancreatic tissue.

TWO CASE STUDIES THAT OFFER HOPE

In September, scientists from Shanghai reported that a 25-year-old woman with Type 1 diabetes had started producing her own insulin within three months of a transplant of reprogrammed stem cells. The researchers extracted the cells from the patient and reverted them into a pluripotent (cells which can differentiate into any cell type) state, and subsequently used them to generate islet cells. About 1.5 million of these cells were injected into the abdominal wall muscles. It has been over a year and the woman is maintaining normal blood sugar level without insulin injections.

However, she was already on immunosuppressants because of a prior liver transplant, which may have helped the cells to survive. Two other patients will also complete a year in November this year. Whether the cells can escape rejection and autoimmunity (which already exists in people with Type 1 diabetes) remains to be seen. Studies from Boston using stem cells but with different approaches — embryonic stem cells or donor stem cells placed in a device to protect them from immune system attacks — are in advanced stages.

This report was preceded by another study in April, where scientists reported successful transplantation of insulin-producing islets into the liver of a 59-year-old man with long-standing Type 2 diabetes. The islets were derived from reprogrammed stem cells taken from the man’s own body. Instead of the pluripotent stem cells that were used in the aforementioned patient of type 1 diabetes, they used intermediate stem cell types (endoderm stem cells, which can differentiate into certain types of cells including pancreatic cells).Insulin was withdrawn within three months and the oral antidiabetic medications were discontinued in about a year.
The derivation of islet tissues from stem cells provides unprecedented new sources for treating diabetes.

However, challenges remain. There is a theoretical risk of uncontrolled proliferation/tumour formation. Whether there is a requirement of life-long immunosuppression in patients receiving stem cell transplants is being studied. There is hope that stem cell-based approaches may reduce the need for immune-suppression or even eliminate it. Both types of diabetes also pose unique challenges. In Type 1 diabetes, there can be ongoing autoimmunity, which can potentially damage transplanted cells. In Type 2 diabetes, a transplant will only help those whose major problem is insulin deficiency rather than insulin resistance.
Larger studies are needed to determine long-term efficacy.

(Dr Mithal is chairman, endocrinology and diabetes, Max Healthcare)