Sugar out of control: A diabetes clinic at Marwari Hospital

A dozen white mice scurry about in their shoebox-sized cages in a research laboratory in Pune. Biologist Ramesh Bhonde has just pulled them back from the brink of death triggered by uncontrolled diabetes. That achievement by itself will be unlikely to create any stir in medical circles. Life-threatening diabetes in mice has been cured many times by other researchers before.

But Bhonde, at the National Centre for Cell Science (NCCS) in Pune, has now also shown that diabetes in mice may be permanently reversed using stem cells from the bone marrow of other mice with diabetes. The successful results in the mice have bolstered hopes among the NCCS researchers that it may be possible to cure diabetes using a patient?s own bone marrow.

However, the NCCS researchers as well as other doctors have cautioned that the success in mice with artificially created diabetes does not mean that the technique will also work in people with diabetes. ?For the moment, it is only a new ray of hope,? says Bhonde who has spent many years trying to find ways to regenerate cells in the pancreas.

The NCCS study involved injecting bone marrow stem cells into the bloodstream of mice that have lost the insulin-making cells called beta islets in the pancreas. A few days after the transplant, the studies showed that the pancreas in the mice had acquired brand new beta islets.

?This looks interesting, but its relevance to humans isn?t clear yet,? says Dr Vishwanathan Mohan, director of the Diabetes Research Centre in Chennai, who is familiar with the NCCS research. ?Recently there have been nearly 50 scientific papers from outside India reporting the cure of diabetes in mice. But from mice to men is a big jump.?

According to Mohan, the stem-cell strategy may not help the majority of patients with type 2 diabetes, a condition in which the pancreas has enough of insulin-secreting cells. Type 2 diabetes does not result from the absence of insulin, but from the inability of insulin to function. ?However, the work on stem cells is important; even if the proportion of people with type 1 diabetes is very small, the absolute number of those with it in whom the pancreas has lost its source of insulin is still very high,? says Mohan.

Several studies over the past five years have shown that the bone marrow contains stem cells ? a class of cells without a specific identity, but which possess the ability to transform into other cells of the body such as liver cells, or bone cells, or nerve cells, or the insulin-making islets.

So the NCCS finding that stem cells can repair the pancreas is by itself not surprising. The novelty in the study lies in demonstrating that even stem cells from the bone marrow of diabetic animals are good enough to fix the damage. ?Diabetes affects many organs in the body. It is heartening to see that stem cells in the diabetics? bone marrow remain viable,? says Bhonde.

In their experiments, the NCCS team injected mice with a special drug that kills the beta islets in the pancreas. This kind of drug-induced destruction of islets is a standard practice in animal experiments. Within a week of receiving the drug, the mice get severe diabetes ? their blood sugar levels soar.

The NCCS researchers extracted bone marrow from diabetic mice, separated the stem cells and injected them into the tail veins of other diabetic mice. Sugar levels in the diabetic mice returned to normal within a week. The mice that did not receive stem cell transplants or that received ?sham injections? as placebo died. But all the mice that received stem cells recovered from diabetes.

Examinations showed that a damaged pancreas acquires a fresh cluster of the beta islets. Reporting their findings in the journal Biochemical Biophysical Research Communications, the NCCS team say multiple injections at regular intervals led to restoration of normal blood sugar. The stem cells from mice with diabetes retain their potential to induce pancreatic regeneration on transplantation.

?When the stem cells enter the bloodstream, a homing system goes into operation. We don?t know exactly what it is ? but something guides the stem cells to the organ that is malfunctioning ? in this case, it?s the pancreas,? says Bhonde.

Scientists have no doubt that cells can sense the presence of other similar cells. Bhonde cites the example of what happens when scientists inject insulin-secreting cells into a mouse with a normal pancreas. The extra insulin should cause sugar levels in the mouse to plummet, and push the animal into a hypoglycaemic state. But that doesn?t happen. The introduction of the additional insulin-secreting cells signals the pancreatic cells to commit suicide so as to maintain normal levels of insulin.

In the same manner, the stem cells transplanted into the diabetic mice stop regenerating when the required number of beta islets have been produced. ?They correct the defect but do not overpopulate the pancreas,? says Bhonde.