Adele Soltani1, Masoud Soleimani2, Mohammad Adel Ghiass3, Seyed Ehsan Enderami4, Shahram Rabbani5, Arefeh Jafarian6, Abdolamir Allameh7. 1. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 2. Tissue Engineering and Hematology Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Shahid Beheshti University of Medical Sciences, School of Advanced Technologies in Medicine, Tissue Engineering and Nanomedicine Research Center, Tehran, Iran. 3. Tissue Engineering Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 4. Immunogenetics Research Center, Department of Medical Biotechnology, Faculty of Advanced Technologies in Medicine, Mazandaran University of Medical Science, Sari, Iran. 5. Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Science, Tehran, Iran. 6. Iranian Tissue Bank and Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: a-jafarian@sina.tums.ac.ir. 7. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: Allameha@modares.ac.ir.
Abstract
AIMS: Cell-based therapy is a promising approach for the treatment of type-1 diabetes mellitus. Identifying stem cells with differentiation potential to Insulin-producing cells (IPCs) and their application is an emerging issue. Different strategies have been used to support cell survival and their specific functions to control hyperglycemia conditions. Novel technologies using appropriate materials/fibers can improve cell transplantation. MAIN METHODS: In the present study, IPCs were differentiated from adipose-derived stem cells transduced with miR-375 and anti-miR-7. The cells' survival rate was also improved using a microfluidic system before their in vivo transplantation. KEY FINDINGS: After adopting a stable, functional condition of the IPCs, the cells were used for in vivo grafting to diabetic mice, which resulted in a substantial drop in blood glucose during four weeks of grafting compared to the control group (p < 0.0001). The pattern of blood glucose levels in the mice receiving fiber entrapped IPCs, was similar to that of non-diabetic mice. Blood insulin was elevated in diabetic mice which received a transplant of fiber-entrapped-IPCs carrying miR-375 and anti-miR-7 after five weeks of transplantation compared to the diabetic mice (p < 0.014). SIGNIFICANCE: For the first time, this study showed that the two-component microfluidic system is useful for supporting the Collagen-Alginate fiber-entrapped IPCs and the miRNA-based cell therapy. Overall, our data show that the IPC encapsulation using a microfluidic system can support the cells in terms of morphology and biological function and their efficiency for controlling the hyperglycemia condition in diabetic mice.
AIMS: Cell-based therapy is a promising approach for the treatment of type-1 diabetes mellitus. Identifying stem cells with differentiation potential to Insulin-producing cells (IPCs) and their application is an emerging issue. Different strategies have been used to support cell survival and their specific functions to control hyperglycemia conditions. Novel technologies using appropriate materials/fibers can improve cell transplantation. MAIN METHODS: In the present study, IPCs were differentiated from adipose-derived stem cells transduced with miR-375 and anti-miR-7. The cells' survival rate was also improved using a microfluidic system before their in vivo transplantation. KEY FINDINGS: After adopting a stable, functional condition of the IPCs, the cells were used for in vivo grafting to diabeticmice, which resulted in a substantial drop in blood glucose during four weeks of grafting compared to the control group (p < 0.0001). The pattern of blood glucose levels in the mice receiving fiber entrapped IPCs, was similar to that of non-diabeticmice. Blood insulin was elevated in diabeticmice which received a transplant of fiber-entrapped-IPCs carrying miR-375 and anti-miR-7 after five weeks of transplantation compared to the diabeticmice (p < 0.014). SIGNIFICANCE: For the first time, this study showed that the two-component microfluidic system is useful for supporting the Collagen-Alginate fiber-entrapped IPCs and the miRNA-based cell therapy. Overall, our data show that the IPC encapsulation using a microfluidic system can support the cells in terms of morphology and biological function and their efficiency for controlling the hyperglycemia condition in diabeticmice.