Type 1 Diabetes Mellitus (Acute Stage) (DM)
Type 1 Diabetes Mellitus(Type 1 DM) is a chronic autoimmune disorder, in which the immune system attacks the body’s own insulin-secreting β-cells (islet cells) in the pancreas.
Damage to pancreatic β-cells leads to insulin deficiency, a hormone required for the cells to metabolize glucose and for maintaining blood glucose level. Type 1 DM is predominately found among kids. Symptoms of patients with Type 1 DM result from elevated blood sugar levels, including frequent urination, increased thirst and hunger, weight loss, blurry vision, tiredness, and slow wound healing. If left untreated and uncontrolled, Type 1 DM cause short-term complications such as ketoacidosis and coma and long-term complications such as cardiovascular disease, stroke, kidney failure, eye damage and foot ulcers.
Type 1 DM is caused by the destruction of β-cells by the host’s own immune system. However, factors that trigger the autoimmune response are not clear. Potential trigger factors may include genetic factors, environmental factors and chemical agents. The exact number of people affected globally by Type 1 DM is unknown while an estimated 1-3 million people are affected each year in the United States. Prevalence of this disease varies across the globe with one case per 100,000 people per year in East Asia and about 30 cases in Northern Europe. There are no known ways to prevent Type 1 DM.
The main treatment for Type 1 DM patients is life-long insulin injection to control hyperglycemia. Insulin is administered subcutaneously via a syringe or a pump multiple times a day. The exact dose of insulin appropriate for each injection depends on the content of the meal/snack, the individual person's sensitivity to insulin, and duration and intensity of physical activity. In addition to insulin, patients often make major lifestyle changes facilitating stabilization of blood sugar level. Despite treatment, a significant number of patients eventually develop disabling sequelae including ketoacidosis, angiopathy, and neuropathy.
Recently, whole pancreas or isolated islet cells transplantation have emerged as a promising treatment restoring normal insulin production. Transplantation of the whole pancreas is rare and recommended only in the patient who also requires a kidney transplant. Pancreatic islets isolated from a donor's pancreas, then injected into the recipient’s portal vein from which they implant onto the recipient’s liver. Accumulated data has shown that over 60% of patients have achieved insulin independence five years after transplantation. Like other organ transplantation, both procedures are critically limited by availability of donors. For patients where a donor is available, they also need lifelong immunosuppressive therapy therefore potential immunodeficiency to prevent transplant rejection.
Advances in Stem Cell Therapy for Acute Phase Type 1 Diabetes Mellitus
Current progress in regenerative medicine has shown that human induced pluripotent stem cells (hiPSCs) can be differentiated into insulin-producing cells (IPCs) in an environment that mimic normal pancreas development. Those IPCs, after transplantation, are shown to respond to changing blood glucose level in animal models. T-MSCs are multipotent stem cells that theoretically can be transdifferentiated into IPCs, or islet organoids, in vitro under a proper induction environment, which makes it a potential regenerative therapy for Type 1 DM.
Compared to adult tissues and adult tissue stem cells, T-MSCs express significantly lower levels of human leukocyte antigens (HLAs), supporting a lower immunogenicity. Therefore, patients with transplantation of T-MSCs derived IPCs might face lower transplant rejection and immunosuppressive treatment.
T-MSCs have immunomodulatory functions and trophic capabilities that may positively regulate autoimmunity, lower pro-inflammatory response, potentially ameliorate damages to pancreatic β-cells, and lead to clinical benefit. In preclinical studies, ImStem has demonstrated T-MSCs can target inflammatory tissues and potentially decrease autoimmunity. More studies are needed to investigate the efficacy of T-MSCs preventing β-cell damage and restoring β-cell functions in DM animal models.