Abstract: TH-PO1182
Senescent and Osteogenic Phenotype of Perirenal Adipose-Derived Mesenchymal Stem Cells in a Rat Model of CKD
Session Information
- CKD: Mechanisms, AKI, and Beyond - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Bragado García, Elvira, Universidad Complutense de Madrid, Madrid, Community of Madrid, Spain
- Palma Guzmán, Paloma, Universidad Complutense de Madrid, Madrid, Community of Madrid, Spain
- Sanz-Gómez, Marta, Universidad Complutense de Madrid, Madrid, Community of Madrid, Spain
- Kreutz, Reinhold, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany
- Plaza de la Fuente, Adrián, Universidad CEU San Pablo, Madrid, Community of Madrid, Spain
- Merino, José Joaquín M, Universidad Complutense de Madrid, Madrid, Community of Madrid, Spain
- Fernandez-Alfonso, Maria S., Universidad Complutense de Madrid, Madrid, Community of Madrid, Spain
Group or Team Name
- GESCAMET.
Background
Chronic kidney disease (CKD) promotes arterial stiffness and vascular calcification. In patients with stage III CKD, elevated plasma levels of the pro-calcifying bone morphogenetic protein 2 (BMP-2) have been reported by our group. Similarly, in the Munich Wistar Frömter (MWF) rat model of CKD, increased BMP-2 levels have been detected in plasma, kidney, and perirenal adipose tissue (PRAT). Given the potential paracrine influence of PRAT on the kidney and renal arteries, we hypothesize that adipose-derived mesenchymal stem cells (ADMSCs) contribute to renal and vascular injury in CKD through the production of profibrotic and pro-calcifying factors.
Methods
ADMSCs were isolated from PRAT of 22-week-old MWF rats and characterized by flow cytometry, transmission electron microscopy, and quantitative PCR (qPCR).
Results
ADMSCs from both rat strains expressed the mesenchymal marker CD90 and lacked the hematopoietic marker CD45. MWF-derived ADMSCs showed lower expression of osteogenic (Runx2, Alp), adipogenic (Pparγ, Lpl), and profibrotic (Tgfβ) genes compared to Wistar controls. However, MWF ADMSCs exhibited significantly enhanced osteogenic differentiation, as demonstrated by increased calcium phosphate deposition by alizarin red staining. Additionally, these cells showed pronounced mitochondrial morphological abnormalities and increased p16 expression, a senescence marker which arrests cell cycle in the G1 phase. This correlates with a reduced ADMSCs proliferation in the MWF group.
Conclusion
In the MWF model of CKD, ADMSCs exhibit a more senescent phenotype and enhanced osteogenic differentiation potential, suggesting a role in the pro-calcifying microenvironment characteristic of CKD.
Funding
- Government Support – Non-U.S.