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. 1. Introduction 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 80–90% 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
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