Stem cells (Dayton, Ohio)Aug 1, 2026

Using Stem Cells and Empagliflozin to Improve Cell Recycling and Protective Proteins in Diabetic Kidney Disease

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 3, 2026

Abstract

MSC therapy improved hyperglycemia in a time-dependent manner (p < 0.0001).

Bone marrow-derived mesenchymal stem cells (MSCs) may decrease albuminuria in a diabetic kidney disease model.
Modest improvements in estimated glomerular filtration rate (eGFR) were observed, despite persistent weight gain.
Treatment with MSCs appeared to modulate early autophagy hyperactivation, as indicated by changes in LC3 protein expression (p < 0.05).
Klotho expression was maintained through MSC therapy, which is associated with reduced oxidative stress (p < 0.05).
The combination of MSCs, empagliflozin, and calorie restriction may present a promising approach for diabetic kidney disease.

Simplified

Diabetic kidney disease (DKD), the leading cause of end-stage renal disease, involves injury across multiple renal compartments. Autophagy dysregulation is a key pathogenic mechanism and may reduce Klotho, a renoprotective protein diminished in DKD. This study evaluated whether bone marrow-derived mesenchymal stem cells (MSCs), combined with empagliflozin and calorie restriction, could modulate autophagy and preserve Klotho expression in DKD. Male BTBRob/ob mice, a leptin-deficient model that develops diabetes and DKD in a progressive manner, were assigned to experimental groups and euthanized at 14-15 or 18-20 weeks. Kidney tissues were analyzed by qPCR, Western blot, and immunohistochemistry. MSCs therapy improved hyperglycemia in a time-dependent manner (p < 0.0001), decreased albuminuria, and modestly improved eGFR, though weight gain persisted. Treatment modulated LC3 protein expression in cortical and medullary regions (p < 0.05), suggesting attenuation of early autophagy hyperactivation. It also helped maintain Klotho expression, correlating with reduced oxidative stress (p < 0.05). Overall, MSCs combined with empagliflozin and calorie restriction show promise as a translational approach for DKD, warranting further long-term preclinical studies.

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Using Stem Cells and Empagliflozin to Improve Cell Recycling and Protective Proteins in Diabetic Kidney Disease

Abstract

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