Int J Stem Cells.  2016 May;9(1):79-89. 10.15283/ijsc.2016.9.1.79.

Study of the Effect of Route of Administration of Mesenchymal Stem Cells on Cisplatin-Induced Acute Kidney Injury in Sprague Dawley Rats

• Moustafa F
• Sobh MA
• Abouelkheir M
• Khater Y
• Mahmoud K
• Saad MA
• Sobh MA

• KMID: 2164164
• DOI: http://doi.org/10.15283/ijsc.2016.9.1.79

Abstract

BACKGROUND AND OBJECTIVES
Mesenchymal stem cells (MSCs) have been shown to ameliorate cisplatin-induced acute kidney injury (AKI). The present study compares the efficacy of different routes of MSCs administration on kidney damage and regeneration after cisplatin-induced AKI.
METHODS
A single intraperitoneal injection of cisplatin (5 mg/kg) was used to induce AKI in 160 rats. MSCs (5×106) were given by either intravenous, intra-arterial or kidney sub capsular injection one day after cisplatin injection. Suitable control groups were included. Rats were sacrificed at 4, 7, 11 and 30 days after cisplatin injection. Kidney function parameters, kidney tissue oxidative stress markers, and scoring for renal tissue injury, regeneration and chronicity were all determined.
RESULTS
MSCs by any routes were able to ameliorate kidney function deterioration and renal tissue damage induced by cisplatin. The overall results of the three routes were equal. Differences between the different routes in one parameter were transient and inconsistent with other parameters.
CONCLUSION
Changing the route of MSCs injection does not have a major influence on the outcome. Future evaluation should focus on differences between the routes of administration considering the long term safety.

Keyword

Acute kidney injury; Cisplatin; Mesenchymal stem cells; Routes of administration; Sub capsular

MeSH Terms

Acute Kidney Injury*
Animals
Cisplatin
Injections, Intraperitoneal
Kidney
Mesenchymal Stromal Cells*
Oxidative Stress
Rats
Rats, Sprague-Dawley*
Regeneration
Cisplatin

Figure

• 

  Fig. 1 Changes in serum creatinine (A), BUN (B), creatinine clearance (C), serum calcium (D), and serum albumin (E) in rats after cisplatin administration and treatment with stem cells (SC) through different routes (n=5 in each group for each time). Significant difference (p<0.05) *versus control, †versus cisplatin, ‡versus i.v. SC; §versus sub-capsular SC. Abbr.: IA: intra-arterial, IV: intravenous, SC: sub capsular.

• 

  Fig. 2 Histological changes of the outer stripe of the outer medulla (OSOM) in the rat kidney after 4 (A~D) and 30 (E~H) days of cisplatin injection (H&E). In comparison to normal OSOM (I). Cisplatin led to tubular necrosis, degeneration, tubular casts, and cellular debris which were more evident at day 4 (A). The necrotic changes were attenuated while regenerative changes were enhanced when bone marrow mesenchymal stem cells were injected via the renal artery (B), the tail vein (C), or under the capsule of the kidney (D). Dilated tubules, some regenerating large tubules, and mild peritubular fibrosis without evidence of necrosis were all evident the cisplatin-treated group by the day 30 (E) but were much attenuated with bone marrow mesenchymal stem cells therapy in the renal artery (F), the tail vein (G), or under the capsule of the kidney (H). BrdU-labeled MSCs were traced 11 days after being injected under the capsule of the kidney (J). Cells were detected in the injured OSOM and few cells were integrated in the tubular epithelium. Magnification: ×100 (B, C, E~I); ×200 (A, D); ×400 (J).

Reference

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