Stem cells based therapies for diabetes

Achieving normal glycaemia is the goal of all diabetes therapy.

Potentially, there are many ways to achieve this goal, including transplantation of cells exhibiting glucose-responsive insulin secretion. However, to be applicable to the large number of people who might benefit from stem cells replacement, an unlimited supply of stem cells must be found. Those cells can then be stored by using a cord blood banks or stem cells banks.

To address this problem, cell lines from human endocrine pancreas have been developed.

In one case, a cell line has been developed from human islets that can be induced under some circumstances to differentiate into functional stem cells exhibiting appropriate glucose-responsive insulin secretion. Inducing differentiation is complex, requiring the activation of multiple signalling pathways, including those downstream of those involved in cell-cell contact and the glucagon-like peptide receptor. In addition, transfer of the PDX gene is also necessary to render the cells competent for differentiation. However, it is clear that many other genes are involved in maintaining the commitment of stem cells towards the cell lineage. Understanding the complement of genes required to establish and maintain a stem cell lineage commitment would be enormously helpful in efforts to develop a cell line that can be used for stem cells replacement therapies.

Here, we provide further information on the characteristics of cell lines that we have developed from the human pancreas that are relevant to the development of a stem cell replacement therapy for diabetes.

The recent explosion of interest in cell replacement therapies for diabetes has been driven primarily by the dramatic progress in allogeneic islet cell transplantation. For the first time, the Edmonton group demonstrated that islet transplantation is a viable therapy for diabetes. This advance was dependent largely on progress in immunosuppressive drug therapy that allowed for a steroid-free regimen. Further advances in this area are likely to result in even better long term results as there is evidence that even the current improved drug regimens are toxic to stem cells, albeit to a lesser extent than the previous steroid containing regimens.

While the success of the Edmonton trial was an important proof of principle, it did not address the major problem with islet transplantation, that is, the grossly inadequate supply of cadaveric pancreas as a source of islets. Solving this problem has been a major focus of research in stem cells biology.

Many different potential sources of cells for stem cells replacement, each with its own advantages and disadvantages, are being studied.