Int J Stem Cells.  2016 May;9(1):70-78. 10.15283/ijsc.2016.9.1.70.

Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats

Affiliations
  • 1Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
  • 2Zoology Unit-, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
  • 3Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
  • 4Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. zohoor26203@yahoo.com
  • 5Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, Egypt.
  • 6Department of Public Health, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
  • 7Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Abstract

BACKGROUND AND OBJECTIVES
Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested.
METHODS
80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately.
RESULTS
hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4.
CONCLUSION
hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity.

Keyword

Cisplatin; nephrotoxicity; Human amniotic fluid Stem cells; Oxidative stress

MeSH Terms

Acute Kidney Injury
Amniotic Fluid
Animals
Atrophy
Cisplatin
Creatinine
Female
Fibrosis
Glutathione
Humans
Kidney
Malondialdehyde
Mesenchymal Stromal Cells*
Necrosis
Oxidative Stress
Rats
Rats, Sprague-Dawley*
Stem Cells
Superoxide Dismutase
Cisplatin
Creatinine
Glutathione
Malondialdehyde
Superoxide Dismutase

Figure

  • Fig. 1 Day 4: (A) Pathological changes in cisplatin injected rats (group I) at day4 shows necrotic dilated tubules in outer strip outer medulla (OSOM) where the tubules are dilated with thin denuded lining epithelium with Marked degenerative changes. It varied from tubular cell vacuolar degeneration, up to complete tubular necrosis and shedding of tubular cells (6~10 tubules/HPFs) (H&E ×200). (B) Histopathologic changes in hAFSCs-treated rats sacrificed after 4 days, OSOM shows less tubular necrosis with focal tubular dilation and occasional mitosis Mild regenerative changes were also detected in OSOM in the form of some regenerating tubules (5%) lined by large cells with prominent nucleoli and with occasional mitotic figures. No solid sheets were detected (H&E ×200).

  • Fig. 2 Day 11: (A) kidney sections obtained from cisplatin injected rats at the 11th day revealed that the degenerative changes varied from tubular cell vacuolar degeneration, up to complete tubular necrosis. Also there was mild interstitial round cell infiltrate. Regenerative changes were also detected and varied from tubular cell enlargement with regenerative atypia, mitosis and interstitial solid sheet formation (H&E ×200). (B) Kidney sections obtained from cisplatin injected rats treated with hAFSCs via tail vein and scarified at the 11th day revealed necrotic tubules with tubular dilatation (1~2 tubules/HPFs). Regenerative changes were detected in the form of solid sheets (3/10 HPFs), mitosis (1~2/10 HPFs) and presence of regenerating tubules. The interstitium was the seat of solid sheets and round cell infiltration (H&E ×200).


Reference

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