Diabetes mellitus is a growing epidemic with a hefty physical, emotional and financial burden. According to the US Centers for Disease Control and Prevention, 29 million Americans suffer from diabetes. Present treatment regimens aim at improving glycemic control with an associated risk of hypoglycemic incidents. This is one of the most important problems accompanying diabetes treatments and can affect a patient’s quality of life due to associated complications. Hence, it became imperative for researchers to explore different therapeutic approaches.

What Transplantation Strategies Are There?

One potential strategy involves a whole organ pancreas transplantation or islet transplantation which can restore endogenous insulin secretion and improve microvascular complications. However, such transplantations expose patients to both surgical complications and the consequences of immune suppression including opportunistic infections and the side effects of immunosuppressant medications.

In response to such complications, research is focusing on the development of artificial organs that can carry out fundamental processes without the risk of rejection or need for immunosuppressing drugs. In a recent paper published in Diabetologia on June 30th of this year, researchers from the University of Cambridge reported that an artificial pancreas may be available for transplantation by 2018.

Targeting the Decreasing β-Cell Mass

Absolute or relative loss of pancreatic β-cells (β-cell mass) is a key pathophysiological event participating in the development of both types of diabetes (type 1 and 2). A novel therapeutic strategy showing promising results involves replenishing the deficit in the β-cell mass. In the past few decades, a number of regenerative approaches to increase the β-cell mass have emerged during preclinical studies. These approaches include but are not limited to β-cell replacement therapy from stem cells, reprogramming of various non-β cell types and the induction of replication of existing β-cells.

Are Stem Cells the Answer?

Differentiation of embryonic pluripotent stem cells (EPSCs) into functional β-cells has raised tremendous interest and hope that it may provide a therapeutically relevant strategy to replace β-cell loss and ameliorate insulin dependence iinsn diabetes. Currently, protocol refinements for the differentiation of EPSCs into mature functional β-cells remains an area under intense investigation. Although many researchers have reported the successful generation of β-cells from human EPSCs in-vitro, further studies are needed to address whether transferring these cells to humans will yield a viable therapeutic option capable of maintaining appropriate β-cell function and mass.

Subsequently, the discovery of the use of induced pluripotent stem cells (iPSC) and mesenchymal adult stem cells (MSC) opened the possibility for isogenic cell therapies. Such strategies avoid the complications of immune rejection and also circumvent some ethical issues with harvesting human embryonic stem cells. Many biotech stem cell products are under clinical testing and, so far, the results are encouraging.

Can Non-Insulin Secreting Cells Be Reprogrammed to Produce Insulin?

New studies in animal models support the possibility of the direct reprogramming of non-β-cell types into insulin-producing and insulin-secreting lineages in-vitro. Recently, researchers from the Diabetes Research Institute at the University of Miami – Miller School of Medicine reported the ability to reprogram non-insulin producing pancreatic cells into insulin producing cells. Other interesting studies reported the successful conversion of skin cells and stomach cells into insulin producing cells. Naturally, more studies are needed in these reprogramming approaches to establish a solid therapeutic potential and long-term feasibility as a β-cell replacement strategy in diabetic patients.

In conclusion, the many efforts intended to control and perhaps cure diabetes mellitus are encouraging. Only time will tell if any of these attempts will be of real clinical relevance and make it to/passed clinical trials.

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