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Updated: Dec 15, 2025
A Novel Clinical Grade Isolation Method for Human Kidney Perivascular Stromal Cells
Published on: August 7, 2017
Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells
Seo Rin Kim1, Xiangyu Zou1, Hui Tang1
1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Abstract:
Cell stress may give rise to insuperable growth arrest, which is defined as cellular senescence. Stenotic kidney (STK) ischemia and injury induced by renal artery stenosis (RAS) may be associated with cellular senescence. Mesenchymal stem cells (MSCs) decrease some forms of STK injury, but their ability to reverse senescence in RAS remains unknown. We hypothesized that RAS evokes STK senescence, which would be ameliorated by MSCs. Mice were studied after 4 weeks of RAS, RAS treated with adipose tissue-derived MSCs 2 weeks earlier, or sham. STK senescence-associated β-galactosidase (SA-β-Gal) activity was measured. Protein and gene expression was used to assess senescence and the senescence-associated secretory phenotype (SASP), and staining for renal fibrosis, inflammation, and capillary density. In addition, senescence was assessed as p16+ and p21+ urinary exosomes in patients with renovascular hypertension (RVH) without or 3 months after autologous adipose tissue-derived MSC delivery, and in healthy volunteers (HV). In RAS mice, STK SA-β-Gal activity increased, and senescence and SASP marker expression was markedly elevated. MSCs improved renal function, fibrosis, inflammation, and capillary density, and attenuated SA-β-Gal activity, but most senescence and SASP levels remained unchanged. Congruently, in human RVH, p21+ urinary exosomes were elevated compared to HV, and only slightly improved by MSC, whereas p16+ exosomes remained unchanged. Therefore, RAS triggers renal senescence in both mice and human subjects. MSCs decrease renal injury, but only partly mitigate renal senescence. These observations support exploration of targeted senolytic therapy in RAS.
Insights
Renal artery stenosis (RAS) causes kidney cellular senescence. Mesenchymal stem cells (MSCs) improve kidney injury but only partially reduce senescence, suggesting senolytic therapies may be beneficial for RAS.
Area of Science:
- Nephrology
- Gerontology
- Regenerative Medicine
Background:
- Cellular senescence, a state of irreversible growth arrest, can result from cell stress.
- Renal artery stenosis (RAS) is linked to kidney ischemia and injury, potentially inducing cellular senescence.
- Mesenchymal stem cells (MSCs) are known to mitigate certain kidney injuries, but their effect on RAS-induced senescence is unclear.
Purpose of the Study:
- To investigate if RAS induces kidney senescence.
- To determine if adipose tissue-derived MSCs can ameliorate RAS-induced kidney senescence and injury.
- To assess senescence markers in urinary exosomes of patients with renovascular hypertension (RVH) before and after MSC treatment.
Main Methods:
- Mice underwent RAS or sham procedures, with some receiving MSCs prior to analysis.
- Kidney senescence was assessed via senescence-associated β-galactosidase (SA-β-Gal) activity, senescence/SASP markers, fibrosis, inflammation, and capillary density.
- Urinary exosomes (p16+, p21+) were analyzed in human subjects with RVH and healthy volunteers, with RVH patients assessed pre- and post-MSC therapy.
Main Results:
- RAS significantly increased kidney SA-β-Gal activity, senescence, and SASP markers in mice.
- MSCs improved renal function, reduced fibrosis, inflammation, and improved capillary density in RAS mice, but did not fully reverse senescence markers.
- Human RVH patients showed elevated p21+ urinary exosomes compared to controls, with only a slight improvement post-MSC treatment; p16+ exosomes remained unchanged.
Conclusions:
- RAS triggers renal senescence in both murine models and human subjects.
- While MSCs offer therapeutic benefits for RAS-induced kidney injury, their capacity to reverse established renal senescence is limited.
- Targeted senolytic therapies warrant further investigation for managing RAS-associated senescence.
