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Adipose Mesenchymal Stem Cell-Derived Exosomes in Conjunction with Roflumilast Ameliorate Chronic Kidney Disease
Mohamed Ali1, Mohamed H Sherif2, Nashwa Barakat3
1Biochemistry Department, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt.
Abstract:
Adipose mesenchymal stem cell-derived exosomes and the PDE4 inhibitor roflumilast (ROF) are investigated as potential treatments for chronic kidney disease (CKD). The exosomes are extracted and analyzed using electron microscopy and flow cytometry, then employed with ROF for in vivo implantation in a CKD animal model. Animals aredivided into seven groups. Group (I) Control; (II) exosomes; (III) ROF; (IV) Adriamycin (ADR); (V) ADR + exosomes, (VI) ADR + ROF, and (VII) ADR + Exosomes+ ROF. Biochemical serum indicators (creatinine, BUN), antioxidant status (GSH, MDA), and the mRNA expressions of TGF-β1, Smad3, IL-6, BAX, Wnt-7, FN, and miRNA145-5p are determined using qRT-PCR. Histology assessment using H&E staining, ultrastructural observation using TEM, and protein expression in kidney tissue (FN1 and BAX) are assessed. The isolated exosomes showed cup-shaped morphologyand expressed CD81, CD9, and CD63. Exosomes and ROF increased glutathione (GSH) levels while decreasing malondialdehyde (MDA) levels. Further, ROF and exosomes treatment lowered the expression of the apoptotic indicators BAX, the fibrotic markers TGFβ1, Smad3, Wnt7a, and FN1, and the inflammatory marker IL6, and increased the expression of miRNA-145. Moreover, ROF and exosomes improved histological and ultrastructural examination. In conclusion, exosomes and ROF can protect against CKD by reducing apoptosis and fibrosis.
Insights
Adipose mesenchymal stem cell-derived exosomes and roflumilast (ROF) show promise in treating chronic kidney disease (CKD). These treatments reduce apoptosis and fibrosis, offering a protective effect against kidney damage.
Area of Science:
- Biomedical research
- Regenerative medicine
- Pharmacology
Background:
- Chronic kidney disease (CKD) is a progressive condition with limited treatment options.
- Mesenchymal stem cell-derived exosomes and phosphodiesterase 4 (PDE4) inhibitors are emerging therapeutic candidates.
Purpose of the Study:
- To investigate the therapeutic potential of adipose mesenchymal stem cell-derived exosomes combined with roflumilast (ROF) in a CKD animal model.
- To evaluate the effects of these treatments on oxidative stress, apoptosis, fibrosis, and inflammation in kidney tissue.
Main Methods:
- Exosomes were isolated from adipose mesenchymal stem cells and characterized.
- A CKD animal model was established using Adriamycin (ADR).
- Animals were treated with exosomes, ROF, or a combination, and various biochemical, molecular, and histological parameters were assessed.
Main Results:
- Exosome and ROF treatment significantly increased antioxidant levels (GSH) and decreased lipid peroxidation (MDA).
- Combined treatment downregulated apoptotic (BAX), fibrotic (TGF-β1, Smad3, Wnt-7, FN1), and inflammatory (IL-6) markers.
- Histological and ultrastructural analyses confirmed renoprotective effects.
Conclusions:
- Adipose mesenchymal stem cell-derived exosomes and ROF demonstrate significant therapeutic potential for CKD.
- These agents protect against kidney injury by mitigating apoptosis and fibrosis.
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