Cell Therapy for Diabetic Neuropathy

A debilitating consequence of diabetes mellitus (DM) is neuropathy which globally affects between 20 -30% of diabetic patients and up to 50% [1, 2]. The lifetime incidence of diabetic neuropathy (DN) is estimated to be up to 45% for type 2 diabetic patients and 59% for type 1 diabetic patients in USA. The risk of DN rises with age, duration of DM, and vascular disease. Characterized by damages in the arms and legs, peripheral neuropathy is the most common complication of DM. The pathophysiology of DN is promoted by several risk factors: microvascular disease, neural hypoxia, and hyperglycemia-induced effects. At the molecular level, the primary cause of diabetic complications is known to be hyperglycemia, which disrupts cellular metabolism by the formation of reactive oxygen species (ROS). In the aspect of nerve functions, ROS formation increases neuron’s susceptibility to damage. In addition, hyperglycemia impedes production of angiogenic and neurotrophic growth factors, which are necessary for normal function of neurons and glial cells and maintenance of vascular structure. The most common presentation of nerve damage due to the effects of hyperglycemia is neuropathic pain. Peripheral neuropathy may cause foot deformities such as hammertoes and unnoticed sores and infections in the numb areas of the foot. Improperly treated infection frequently extends to the bone and requires an amputation of the foot. There have not been any definitive disease-modifying treatments to reverse DN. The current treatment focuses on tight glycemic control which can reduce potential risk factors for further nerve damage and DN-associated pain management. In many studies, deficiency of neurotrophic factors and lack of vascular support have been regarded as key factors in the development DN. Therefore, cell therapy has recently emerged as an attractive therapeutic strategy to meet the needs of both neurotrophic and vascular deficiencies of DN.