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Adenovirus-Mediated Over-Expression of Nrf2 Within Mesenchymal Stem Cells (MSCs) Protected Rats Against Acute Kidney
Mohammad Mohammadzadeh-Vardin1, Mehryar Habibi Roudkenar2, Ali Jahanian-Najafabadi3
1Department of Anatomical Sciences and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
Purpose:
Recent developments in the field of cell therapy have led to a renewed interest in treatment of acute kidney injury (AKI). However, the early death of transplanted mesenchymal stem cells (MSCs) in stressful microenvironment of a recipient tissue is a major problem with this kind of treatment. The objective of this study was to determine whether overexpression of a cytoprotective factor, nuclear factor erythroid-2 related factor 2 (Nrf2), in MSCs could protect rats against AKI.
Methods:
The Nrf2 was overexpressed in MSCs by recombinant adenoviruses, and the MSCs were implanted to rats suffering from cisplatin-induced AKI.
Results:
The obtained results showed that transplantation with the engineered MSCs ameliorates cisplatin-induced AKI. Morphologic features of the investigated kidneys showed that transplantation with the MSCs in which Nrf2 had been overexpressed significantly improved the complications of AKI.
Conclusion:
These findings suggested that the engineered MSCs might be a good candidate to be further evaluated in clinical trials. However, detailed studies must be performed to investigate the possible carcinogenic effect of Nrf2 overexpression.
Insights
Overexpressing nuclear factor erythroid-2 related factor 2 (Nrf2) in mesenchymal stem cells (MSCs) protected rats against acute kidney injury (AKI). Engineered MSCs improved kidney complications, suggesting potential for clinical trials.
Area of Science:
- Regenerative Medicine
- Cell Therapy
- Nephrology
Background:
- Mesenchymal stem cells (MSCs) show promise for treating acute kidney injury (AKI).
- Early death of transplanted MSCs in the recipient's stressful microenvironment limits their therapeutic efficacy.
- Enhancing MSC survival is crucial for effective cell-based AKI treatment.
Purpose of the Study:
- To investigate if overexpressing the cytoprotective factor nuclear factor erythroid-2 related factor 2 (Nrf2) in MSCs can protect against AKI.
- To evaluate the therapeutic potential of Nrf2-engineered MSCs in a rat model of AKI.
Main Methods:
- Nuclear factor erythroid-2 related factor 2 (Nrf2) was overexpressed in MSCs using recombinant adenoviruses.
- The engineered MSCs were transplanted into rats with cisplatin-induced AKI.
Main Results:
- Transplantation of Nrf2-overexpressing MSCs significantly ameliorated cisplatin-induced AKI in rats.
- Histological examination revealed that engineered MSCs improved kidney morphology and reduced AKI complications.
- Nrf2 overexpression enhanced the survival and protective capacity of MSCs in the AKI microenvironment.
Conclusions:
- Engineered MSCs overexpressing Nrf2 demonstrate therapeutic potential for AKI.
- These findings support further investigation of Nrf2-engineered MSCs in preclinical and clinical settings.
- Further studies are warranted to assess the long-term safety, including potential carcinogenic effects, of Nrf2 overexpression.
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