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Research
Induced Hyperglycemia in Mice is Controlled Following the Microfluidic System- Assisted Transplantation of Stem Cells-derived Insulin-producing Cells Transduced with miRNA
Abdolamir Allameh
Tarbiat Modares University Faculty of Medical Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0757-9572
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Cell-based therapy is a promising approach for the treatment of type 1 diabetes mellitus. Identification of stem cells as progenitor stem cells with differentiation potential to Insulin-producing cells (IPCs) and their application is an emerging issue. Different strategies have been used to support the cell survival and their specific functions to control hyperglycemia condition. Novel technology systems using appropriate materials/fibres can improve the cell transplantation.
Methods
In the present study, glucose-sensitive insulin-producing cells (IPCs) were differentiated from adipose-derived stem cells (ADSCs) transduced with miR-375 and anti-miR-7 to enhance the functions of the cells. The survival rate of the cells was also improved by using a microfluidic system prior to in vivo transplantation of the IPCs. The contribution of miR-375 with the anti-miR-7 in mature IPCs derived from ADSCs resulted in gaining the function of the cells as judged by insulin production
Results
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 (5-folds) in blood glucose during four weeks of grafting. The pattern of blood glucose levels in the mice receiving fiber entrapped IPCs was similar to that of non-diabetic mice and blood glucose declined in animals treated with fiber-entrapped-IPCs. Blood insulin was elevated (2-folds) in diabetic mice received transplant of fiber-entrapped-IPCs carrying miR-375 and anti-miR-7 after five weeks of transplantation when compared to the untreated diabetic mice. 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 miRNAs-based cell therapy.
Conclusions
Overall data show that the IPCs encapsulation by the microfluidic system can support the cells in terms of morphology and biological function and their efficiency for controlling the hyperglycemia condition in diabetic mice.
Keywords
Anti-miR-7, IPCs, Diabetes, Encapsulation, Microfluidics, miR-375
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This is a preprint. It has not completed peer review.
Research
Induced Hyperglycemia in Mice is Controlled Following the Microfluidic System- Assisted Transplantation of Stem Cells-derived Insulin-producing Cells Transduced with miRNA
Abdolamir Allameh
Tarbiat Modares University Faculty of Medical Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0757-9572
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 18 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Cell-based therapy is a promising approach for the treatment of type 1 diabetes mellitus. Identification of stem cells as progenitor stem cells with differentiation potential to Insulin-producing cells (IPCs) and their application is an emerging issue. Different strategies have been used to support the cell survival and their specific functions to control hyperglycemia condition. Novel technology systems using appropriate materials/fibres can improve the cell transplantation.
Methods
In the present study, glucose-sensitive insulin-producing cells (IPCs) were differentiated from adipose-derived stem cells (ADSCs) transduced with miR-375 and anti-miR-7 to enhance the functions of the cells. The survival rate of the cells was also improved by using a microfluidic system prior to in vivo transplantation of the IPCs. The contribution of miR-375 with the anti-miR-7 in mature IPCs derived from ADSCs resulted in gaining the function of the cells as judged by insulin production
Results
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 (5-folds) in blood glucose during four weeks of grafting. The pattern of blood glucose levels in the mice receiving fiber entrapped IPCs was similar to that of non-diabetic mice and blood glucose declined in animals treated with fiber-entrapped-IPCs. Blood insulin was elevated (2-folds) in diabetic mice received transplant of fiber-entrapped-IPCs carrying miR-375 and anti-miR-7 after five weeks of transplantation when compared to the untreated diabetic mice. 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 miRNAs-based cell therapy.
Conclusions
Overall data show that the IPCs encapsulation by the microfluidic system can support the cells in terms of morphology and biological function and their efficiency for controlling the hyperglycemia condition in diabetic mice.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7