The Promising Role of hypoxia-resistant insulin-producing Cells in Ameliorating Diabetes Mellitus In Vivo

Abstract

Aim: This study aimed to evaluate the efficacy of hypoxia-persistent insulin-producing cells (IPCs) against diabetes in vivo. Materials & methods: Mesenchymal stem cells (MSCs) differentiation into IPCs in the presence of Se/Ti (III) or CeO₂ nanomaterials. IPCs were subjected to hypoxia and hypoxia genes were analyzed. PKH-26-labeled IPCs were infused in diabetic rats to evaluate their anti-diabetic potential. Results: MSCs were differentiated into functional IPCs. IPCs exhibited overexpression of anti-apoptotic genes and down-expression of hypoxia and apoptotic genes. IPCs implantation elicited glucose depletion and elevated insulin, HK and G6PD levels. They provoked VEGF and PDX-1 upregulation and HIF-1α and Caspase-3 down-regulation. IPCs transplantation ameliorated the destabilization of pancreatic tissue architecture. Conclusion: The chosen nanomaterials were impressive in generating hypoxia-resistant IPCs that could be an inspirational strategy for curing diabetes.

Plain Language Summary

Transplantation of cells that can release insulin have been reported as an alternate method to islet transfer for curing diabetes; however, the main difficulty facing the quality of the pancreatic cells is the deficiency of oxygen. Thus, this study was done to discover a new curing method for diabetes by producing cells that can release insulin and could survive under low oxygen circumstances, and assessing their healing ability against diabetes in rats.

Graphical abstract

Keywords:

• diabetes mellitus
• hypoxia
• insulin-producing cells
• mesenchymal stem cells
• nanomaterials

Author contributions

HH Ahmed: conceptualization, investigation, data validation, funding acquisition, project administration, resources, writing – review & editing; HA Aglan: methodology, writing - review & editing, data validation, formal analysis; HH Beherei: investigation, formal analysis; M Mabrouk: investigation, formal analysis; NS Mahmoud: methodology, formal analysis, writing – original draft, data validation; visualization. All authors wrote, revised and approved the final manuscript and agreed to be accountable for all aspects in the study concerned with either the accuracy or integrity of any part of the study.

Acknowledgments

The authors appreciate the effective participation of Prof. Youssef Fawzy (Animal Reproduction Department, National Research Centre, Egypt) in the histological investigation of this work.

Financial & competing interests disclosure

This work received financial support from the National Research Centre, Egypt (grant no.: 11010134). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was conducted according to the guidelines of the laboratory animal care and use and was approved by the Ethical Committee of the Medical Researches of the National Research Centre, Egypt (approval no. 16386), complying with the ARRIVE guidelines and was performed according to the National Institutes of Health Guide for the Care and Use of Experimental Animals (NIH publications no. 8023, revised 1978).

Data availability statement

The authors declared that all the data had been included in the manuscript, and the data could be obtained from the corresponding author upon reasonable request.