Times of India
5 June 2008
Pune, India
By Umesh Isalkar

In what could be termed as hope enwrapped in golden hypothesis for diabetic patients across the globe, a city–based scientist from National Centre for Cell Science (NCCS), Anandwardhan Hardikar is studying the potential of pancreatic islet–derived mesenchymal cells, which he claims, have close resemblance to precursors of insulin producing cells.

Experiments have so far been successfully carried out in mice and Hardikar is presently collaborating with surgeons at the Asian Institute of Gastroenterology (AIG), Hyderabad, to taking these studies further into large animal models and eventually to phase I clinical trials.

“We are now looking at the potential of these mesenchymal cells to cure diabetes in monkeys, only after which we plan to go ahead with human clinical trials,” said Hardikar. “Our studies are in progress and all I can say now is that if you are a mouse, we can cure you using these pancreatic precursor cells,” he said with a glint of confidence in his eyes.

Presently, there is a large debate on in understanding the potential of several ‘Stem cells’, obtained from various sources including the cord blood and bone marrow. In my laboratory, we started by understanding several precursor cells including bone marrow, cord blood, stem cells or other pancreatic duct precursors, but found that these cells have a chromatin (DNA–Protein) conformation that does not allow efficient transcription of insulin gene, said Hardikar.

Thus we may not be able to use these cells for treatment of diabetes unless their chromatin conformation is effectively altered so as to allow efficient production of insulin, explained Hardikar.

“The insulin gene is “Read” by an enzyme (polymerase) to generate a molecule (RNA), which is necessary to produce insulin protein,” he said, adding that this expression of insulin gene is tissue–specific and occurs mostly in the pancreatic islet beta cells, which have a specific (active) chromatin conformation.

In our analysis, we found that adult human bone marrow cells, umbilical cord blood cells and adult pancreatic duct cells have higher inactive state of chromatin conformation at insulin gene promoter stage as compared to the mesenchymal cells that we obtain from adult or foetal insulin–producing islets, he said.

“We found that cells that are isolated from human islets themselves have the (active) promoter conformation that closely resembles that of insulin–producing cells,” said Hardikar. Since these cells are obtained from insulin–producing cells, they are, in my view, the next best candidate for cell replacement therapy in diabetes, apart from adult islets themselves.

The limitation in use of adult islets is the scarcity of donor pancreas. There is, therefore, a need to search for better precursor cells that can be differentiated to insulin–producing cell aggregates. The benefit of using islet–derived mesenchymal cells is that these can be expanded billions of fold and yet be differentiated to insulin–producing isletlike cell aggregates, he explained.

“A well defined plan for safety and efficacy of these cells would help us in the long run to decide the potential of these cells in cell replacement therapy for diabetes,” he said. The work in the laboratory of Hardikar is carried out by funding through the NCCS, Department of Biotechnology, Government of India and UK–India Research Initiative.

Calling it a potential research, city based diabetologist Shailaja Kale said the work has tremendous scope and bright future ahead. “If the work gets through all the phases of clinical trials successfully, it would be a breakthrough research that would eliminate the threat of diabetes, which has assumed an epidemic proportion now,” said Kale.