Enhanced reno-protective effects of CHIR99021 modified mesenchymal stem cells against rat acute kidney injury model
Year: 2024
Type: article
Abstract: Introduction: Mesenchymal stem cells of human umbilical cord origin (hucMSCs) appear to be an attractive candidate for cell-based therapies. However, their efficacy requires improvement as poor survival and specific homing to the site of injury are the major barriers to their effective implementation in cell therapy. As Wnt signaling pathway is involved in the development and repair of organs, we adopted a preconditioning strategy of stem cells by using CHIR99021 compound (a Wnt pathway agonist) to potentiate hucMSCs beneficial effects and circumvent their therapeutic limitations. Methods: We treated hucMSCs with 5 µM of CHIR99021 and evaluated the expression levels of genes involved in different biological processes through qRT-PCR. Subsequently, we examined the effectiveness of preconditioned cells (CHIR99021-hucMSCs) in a cisplatin-induced rat acute kidney injury model. Amelioration in tissue injury was evaluated by histopathology, immunohistochemistry and renal functional assessment. Results: ≤ 0.01) were observed in preconditioned hucMSCs group compared to untreated AKI rats. In addition, administration of preconditioned hucMSCs in kidney injury model offered better restoration of tubular cell membrane β-catenin molecules. Our findings showed that CHIR99021-modified hucMSCs may exhibit better capacity for cell migration and proliferation. Conclusion: The results showed that preconditioning of stem cells with Wnt pathway activators could provide advanced benefits for organ repair, which may contribute to design a more effective therapeutic approach for renal regeneration.
Source: Bioimpacts
DOI: 10.34172/bi.30600
Authors: Rakhshinda Habib, Rabia Farhat, Mohsin Wahid, Jahanara Ainuddin
Institution: Dow University of Health Sciences
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4404705439