Diabetes and Challenges

1. Type 1 diabetes (T1D)

    Type 1 diabetes (T1D) is an autoimmune disease caused by a T cell-mediated destruction of pancreatic islet b cells and thereby limits insulin production and glucose homeostasis. Millions of individuals worldwide have T1D, and the number of individuals with T1D is increasing annually among different populations. While daily insulin injections offer some control over blood sugar levels and may delay the onset of chronic complications due to dysglycemia, insulin injection is not a cure. Ideally, therapeutic approaches to treating or curing T1D should address multiple or all of the underlying causes of autoimmunity in T1D. Unfortunately, the etiology of T1D remains largely unknown in humans. Possible triggers for autoimmunity in T1D include genetic, epigenetic, physical, social, and environmental factors. These factors may act independently or jointly to initiate or potentiate the development of autoimmunity. As is expected in conditions with multiple contributing factors, T1D-related dysfunction in the immune system has been traced to dysfunctions in multiple cell types and targets including T cells, B cells, regulatory T cells (Tregs), monocytes/macrophages, dendritic cells (DCs), natural killer (NK) cells, and natural killer T (NKT) cells. Due to the polyclonal nature of T1D-related autoimmune responses and the global challenges of immune regulation in T1D patients, therapies and trials that only target one or a few components of the autoimmune response are likely to fail just as recent trials involving anti-CD3 antibody for T cells and GAD 65 vaccination have failed. Successful therapies will likely restore immune balance and peripheral tolerance by addressing changes in multiple targets within the immune system. Tianhe has developed an innovative technology based on the stem cell-based immune therapy, designated Stem Cell Educator therapy.

2.  Type 2 diabetes (T2D)

   Type 2 diabetes (T2D) is the most common type of diabetes, with prevalence rates exceeding 12.1% of the population in India, 9.7% in China, and 8.3% in the United States. The incidence of T2D is increasing worldwide due to popularization of a Western lifestyle characterized by overnutrition and limited exercise. Diabetes-associated complications (e.g., cardiovascular diseases, stroke, blindness, kidney failure, and emotional stress) markedly decrease quality of life of T2D patients, limiting the productivity of individuals with the disease and creating significant economic and social burdens. Thus, finding a cure for T2D is a top priority.

    In adults T2D has traditionally been characterized by elevated fasting blood glucose and an abnormal glucose tolerance test without evidence of autoimmune destruction of pancreatic islet b cells. However, evidence collected over the past decade indicates that the etiology of T2D includes a chronic inflammation and an autoimmune component that initiate an inflammation affecting pancreatic islet b cells and insulin sensitivity (Zhao Y, et al. Autoimmunity Reviews 2012), which provides new insight into the mechanism and potential treatment of insulin resistance. These findings suggest T2D may be a candidate for some of the therapies in development for T1D, including the use of stem cell-based regeneration of pancreatic islet b cells and immune modulation by adult multipotent stem cells derived from cord blood or bone marrow. While stem cell transplantation research faces many technical and ethical barriers, the use of adult multipotent stem cells to modulate immune response may provide a more universally acceptable and feasible approach. Notably, we have successfully applied the Stem Cell Educator therapy to treat T2D patients, which have been orally presented at the Scientific Sessions of 72nd American Diabetes Association (ADA, Philadelphia 2012). Our clinical data have been published in a peer review clinical journal BMC Medicine (2013).