Hyaluronic Acid Coated Umbilical Cord Mesenchymal Stem Cells Can Reduce Blood Glucose to Normal and Promote Repair Islets of Diabetic Mice and Activation Wnt/Beta-Catenin Signaling Pathway Effect on Diabetic Mice Cell Therapy and Treatment Mechanism

Type I diabetes is due to autoimmune destruction of pancreatic β cells and lead to inefficient secretion of insulin. Mesenchymal stem cells (MSC) with immune suppression and anti-inflammatory functions, the use of MSC to treat type I diabetes is a very feasible. Human umbilical cord mesenchymal stem cells (hUCMSC) have the CD44 receptor, hyaluronic acid (HA) by combining with the cell surface CD44 with anti-inflammatory and immunosuppressive effects and can inhibit apoptosis. We use HA coated 6 × 106 hUCMSC transplanted into liver capsule of type I diabetic mice, after 4 days treatment, the type I diabetic mice with HA coating hUCMSC treatment can effectively lowering blood glucose to normal 158.57 ± 9.71 mg / dL or so (n = 3), and after 28 days of treatment, the HA coating of hUCMSC in treated mice has maintained the same level of blood glucose with normal mice. After 4 days treatment, the liver of type I diabetic mice with HA coating hUCMSC treatment exist on human nuclear protein, CD44 and ki67 performance. After 28 days of treatment, the islet cells in type I diabetic mice have been damaged and smaller; the islet cells of the HA coating of hUCMSC in treated mice are relatively large. Transplantation of the HA coating of hUCMSC is indeed effective in treating type I diabetic mice, it reduced blood glucose back to normal and promote repair or regeneration of pancreatic islet cells. But alone with hUCMSC to treat type I diabetic mice cannot effectively reduce blood glucose in diabetic mice, may be due to the lack of HA protection led to hUCMSC in high glucose environment cause of hUCMSC damage or apoptosis. Use nanoLC-MS/MS to analyze the hUCMSC protein expression, a total of 4381 proteins are identified in triple analysis. More than 20% of the proteins have been identified as an important signaling pathway with Wnt /β-catenin signaling pathway. The CD44 receptor is regulated by the activation Wnt /β-catenin pathway, and CD44 is hUCMSC-specific marker. High blood glucose inhibits the Wnt /β-catenin signaling. Under high blood glucose environment, our hypothesis is through the activation of Wnt /β-catenin pathway can reduce hUCMSC apoptosis, leading to an increased hUCMSC proliferation in order to treat type I diabetic mice and can effectively reduce their blood glucose levels and promote repair or regeneration of pancreatic islet cells. The first year of research goal is to establish a stable and reliable type I diabetic animal models by using Streptozotocin, and then transplanted the HA coating of hUCMSC to treat type I diabetic mice. The second year goal is to study the treatment mechanism of the HA coating of hUCMSC effective in treating type I diabetes under high glucose environment by using cellular model and through the use of GSK-3β inhibitor BIO to activate intracellular Wnt /β-catenin pathway, can increase hUCMSC proliferation and reduction of apoptosis under high glucose stress. Research objective of the third year is using animal model to study through the use GSK-3β inhibitor BIO to activate Wnt /β-catenin pathway in type I diabetic mice, alone handled by the BIO treated hUCMSC therapy has more effective in treating result of type I diabetic mice.

Project ID:PB10012-0328
External Project ID:NSC100-2221-E182-071