Vascular stem cells in diabetic complications: evidence for a role in the pathogenesis and the therapeutic promise

Diabetes is a chronic and debilitating metabolic disease that presently has no cure. Currently, the total number of people with diabetes is upwards of 221 million and in North America alone, more than 10% of the population is affected [1]. This amounts to a staggering economic burden, estimated to reach $17 billion a year by 2020 in Canada [2], and almost $116 billion in the United States [3]. Although the incidence in North America is quite alarming, close to 80% of diabetes-related deaths occur in low- and middle- income countries due to poor management of complications and lower standards of healthcare [4]. Despite great efforts to combat this disease, the World Health Organization projects that diabetes-related deaths will more than double by the year 2030 [4].The most important discovery in the diabetes field was that of insulin in 1921. Exogenous insulin significantly alleviated diabetic coma and ketoacidosis, and saved millions. However, diabetic patients are still not morbidity-free due to the chronic secondary complications that arise in every diabetic patient. These long-term complications manifest as micro- (retinopathy, neuropathy, nephropathy, and cardiomyopathy) and macro- (atherosclerosis) vascular dysfunctions [5]. Although the clinical features of the complications are quite varied, the underlying cause is an aberration in the vasculature of the target organs. Two major clinical trials paved the way to better understanding the cause of the diabetic complications: the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Perspective Diabetes Study (UKPDS), completed in 1993 and 1997 respectively. In both trials, type 1 and type 2 diabetic patients were put under intensive glycemic control, and in both cases, there was delayed progression and/or inhibition of the onset of diabetic complications [6,7]. It is true that other factors, such as hyperlipidemia and hyperinsulinemia, may contribute to the pathogenesis of diabetic complication