Mitigation of Renal Injury in Wistar Rats Using Adipose Tissue-derived Mesenchymal Stromal Cells and Simvastatin

Abstract

Objective: Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury, negatively impacting short- and long-term kidney transplantation results. No effective treatment is available to protect or treat IRI currently. We aimed to investigate the role of pre-injury oral simvastatin and adipose tissue-derived mesenchymal stem cells (MSC) infusion, alone or in combination, to prevent and treat renal IRI, and to evaluate neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for IRI in a rat model. Materials and Methods: The study was conducted on adult male Wistar rats (n=75, 8-12 weeks old). Rats were divided into the following groups: healthy group (H) (no surgery, no treatment); control (C) (lesion animals + no treatment); oral simvastatin + lesion animals (S); MSC infusion + lesion animals (SC); MSC infusion + oral simvastatin + lesion animals [stem cells plus simvastatin (SC+S)]. Blood samples were collected at days 0, 15, and 30 for measurement of serum creatinine (Cr) and on day 1 for measurement of NGAL protein. The animals were followed up for 30 days, at which time a histopathological analysis was performed. Results: The model used was able to establish IRI, as NGAL levels were significantly higher in the interventional groups. Cr increased at 15 days and returned to baseline, showing a pattern that was significant in the SC+S group. The combination of MSC and simvastatin resulted in lower renal IRI morphologic scores. Conclusion: The combination of pre-injury oral simvastatin and MSC infusion synergistically prevents experimental renal IRI.

Keywords

• basic science
• reconstructive urology
• transplantation and vascular surgery