Mesenchymal Stem Cell Therapy in Diabetes Mellitus …

J Nucleic Acids. 2013; 2013: 194858.

1Zewail University of Science and Technology, 6th of October City, Giza 12588, Egypt

2Urology and Nephrology Center, Mansoura 35516, Egypt

Academic Editor: Sherif F. El-Khamisy

Received 2013 Mar 13; Accepted 2013 Apr 18.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs) therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

Obesity and diabetes are the major health challenges for the twenty first century, according to a recent report by the International Diabetes Foundation. The connection between obesity and diabetes is evident in sharing the same risk factors and the fact that 8090% of type 2 diabetics are also obese. Diabetes is one of the top ten leading causes of death worldwide, according to a recent WHO report [1]. The global prevalence of diabetes in 2012 was estimated to be more than 10% among adults. Of the diabetic population 95% are of type 2, and onset is mainly at an adult age (more than 25 years), with the highest prevalence in the Eastern Mediterranean region and the Americas. Diabetes is the leading cause of renal failure and blindness in advanced countries, and the risk of limb amputation is 10 times higher in diabetic patients. In addition, most diabetic patients develop hypertension and cardiovascular diseases, which account for high rates of morbidity and mortality among adult patients. The disease can be initially treated by oral medication, but eventually, some 27% become insulin dependent. Of these, less than one half achieve the recommended HB A1c level [2], since exogenous insulin cannot provide the tight glycemic control exerted by the pancreas-derived insulin secretion. Replacement of and/or improvements in endogenous cell reserves of the cells would be an ideal therapeutic option.

A milestone in cell-based therapies for diabetes mellitus has been achieved with the application of islet transplantation from cadaveric donors, and the success of the Edmonton protocol back in 1999 [3]. Type 1 diabetic patients had their diseased islets replaced by high quality functioning islets of Langerhans from fresh cadaveric donors. Increased insulin production, normal blood glucose levels and normal glycosylated hemoglobin levels, and insulin independence were achieved. A modified glucocorticoid-free immunosuppressive regimen using low dose of tacrolimus and normal dose of sirolimus maintained graft acceptance and prevented rejection. While in the initial series only 10% of patients maintained an insulin independent state by five years [4], current data from several centers suggest that with potent T-depletion induction and maintenance immunosuppression that rates exceeding 50% insulin independence can now be routinely achieved [5]. However this often requires the use of more than one donor to achieve an adequate islet engraftment mass.

As stem cell therapy gained momentum over the past year, efforts to engineer islet-like cells or insulin producing cells from different types of stem cells have offered an appealing alternative to islet transplants. In principle, stem cell therapy avoids some of the serious drawbacks of islet transplantation, most obviously, the shortage of organ donors. Patients can donate their own stem cells to be expanded and differentiated in vitro into islet producing cells. The autologous cells can then be injected back into the patient, thus avoiding possibilities and complications of graft rejection, and/or a requirement for and immune suppressive regimen. While islet transplantation in an allogeneic environment may suffer cell exhaustion, stem cell therapies potentially provide sustained source of insulin uncompromised by the many debilitating side effects of the immune suppressive drugs when the transplant is autologous. Sources for stem cell therapies in diabetes mellitus are multiple, including embryonic stem cells (ESCs), cord blood stem cells, iPSCs (induced pluripotent stem cells), and adult stem cells derived from adult tissues.

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