Therapeutic efficacy of bone marrow derived mesenchymal stromal cells versus losartan on adriamycin-induced renal cortical injury in adult albino rats.

BACKGROUND: Renal disease is a major health problem. Recent studies have reported the efficacy of stem cell therapy in nephropathy animal models.

AIM OF THE WORK: This study was designed to investigate the therapeutic effectiveness of bone marrow-derived mesenchymal stromal cells (MSCs) versus losartan in the treatment of renal alterations induced by adriamycin (ADR).

MATERIALS AND METHODS: Thirty-five adult male albino rats were divided into four groups. Group I was the control group. Group II (adriamycin-treated group),which included ten rats that were injected with a single dose of adriamycin (15 mg/kg) intraperitoneally, was subdivided into subgroup IIa and IIb and they were sacrificed 1 week and 5 weeks after adriamycin injection, respectively. Group III was the adriamycin + losartan-treated group and 1 week after adriamycin injection five rats received 10 mg/kg of losartan orally and daily for 4 weeks. Group IV was the adriamycin + MSC-treated group); five rats were injected with adriamycin as group II then supplied with MSCs at a dose of 1 × 10(6) cells suspended in 0.5 mL of phosphate-buffered saline (PBS) per rat in the tail vein 1 week after adriamycin injection. Rats of this group were sacrificed 4 weeks after the stem cell injection. Blood urea nitrogen and serum creatinine were measured. Samples from renal cortex were processed for light and electron microscope examination. As regards light microscope, sections were stained with hematoxylin and eosin (H-E), periodic acid-Schiff (PAS), masson trichrome, proliferating cell nuclear antigen (PCNA) and Caspase-3 immunohistochemical stains. Morphometrical and statistical analyses were also conducted.

RESULTS: Examination of adriamycin-treated group revealed deterioration of renal functions and various degrees of renal structural alterations as vacuolated cytoplasm, dark nuclei and detached epithelial lining. Administration of losartan partially improved ADR-induced kidney dysfunction, whereas MSCs denoted a more ameliorative role evidenced by structural and functional recovery.

CONCLUSION: MSCs have a relevant therapeutic potential against ADR-induced renal damage. MSCs may accomplish this role by decreasing caspase-3 expression and increasing proliferating cell nuclear antigen staining which influence the regeneration of the kidney.