Human Engineered Skeletal Muscle Tissue to Treat Insulin Resistance in Type II Diabetes

Diabetes Mellitus type II (DM2) is the most common type of diabetes, widely spread in developed countries and responsible for more than 1 million deaths every year. It is characterized by skeletal tissue insulin resistance and is usually non-insulin dependent. However, progression of the disease can cause various complications, including insulin impairment. Glucose transporter type 4 (GLUT4), mainly expressed in skeletal muscle tissue, is the key factor in glucose homeostasis; Many studies have shown reduction in GLUT4 expression and translocation levels in DM2 patients. Therefore, we hypothesize GLUT4 can be part of the solution. Previous study in our group showed that implantation of GLUT4 over-expressing (GLUT4 OE) mouse skeletal muscle tissue in diabetic mice can improve diabetic markers. To bring the technology closer to the clinic, we aim to implement the concept in human cells. Moreover, to improve patient’s compliance and reduce therapy risks we set out to develop minimally invasive delivery method for the engineered tissue. We have genetically modified human myoblasts to overexpress GLUT4 and successfully grown them on 3D scaffolds. Glucose uptake assays show the engineered tissue has enhanced uptake capacity compared to WT cells. Next, we developed novel, shape-memory scaffold to deliver functional skeletal muscle tissue via injection. The injectable scaffold was fine-tuned to enable skeletal muscle tissue development. Metabolic viability and glucose uptake assays were used to assess tissue viability and functionality post injection. We believe this new concept of DM2 therapy can address earlier stages of the disease and improve patients’ quality of life.