title: Comparative study of allogenic and xenogeneic mesenchymal stem cells on cisplatin-induced acute kidney injury in Sprague-Dawley rats.
abstract: The paracrine and regenerative activities of mesenchymal stem cells (MSCs) may vary with different stem cell sources. The aim of the present study is to compare the effects of MSCs from different sources on acute kidney injury (AKI) induced by cisplatin and their influence on renal regeneration.
  
  
  
  A single intraperitoneal injection of cisplatin (5 mg/kg) was used to induce AKI in 120 Sprague-Dawley rats. Rats were treated with either rat bone marrow stem cells (rBMSCs), human adipose tissue-derived stem cells (hADSCs), or human amniotic fluid-derived stem cells (hAFSCs). 5 × 10(6) MSCs of different sources were administered through rat tail vein in a single dose, 24 hours after cisplatin injection. Within each group, rats were sacrificed at the 4th, 7th, 11th, and 30th day after cisplatin injection. Serum creatinine, BUN, and renal tissue oxidative stress parameters were measured. Renal tissue was scored histopathologically for evidence of injury, regeneration, and chronicity. Immunohistochemistry was also done using Ki67 for renal proliferative activity evaluation.
  
  
  
  MSCs of the three sources were able to ameliorate cisplatin-induced renal function deterioration and tissue damage. The rat BMSCs-treated group had the lowest serum creatinine by day 30 (0.52 ± 0.06) compared to hADSCs and hAFSCs. All MSC-treated groups had nearly equal antioxidant activity as indicated by the decreased renal tissue malondialdehyde (MDA) and increased reduced glutathione (GSH) level and superoxide dismutase (SOD) activity at different time intervals. Additionally, all MSCs improved injury and regenerative scores. Rat BMSCs had the highest count and earliest proliferative activity in the renal cortex by day 7 as identified by Ki67; while, hAFSCs seem to have the greatest improvement in the regenerative and proliferative activities with a higher count of renal cortex Ki67-positive cells at day 11 and with the least necrotic lesions.
  
  
  
  Rat BMSCs, hADSCs, and hAFSCs, in early single IV dose, had a renoprotective effect against cisplatin-induced AKI, and were able to reduce oxidative stress markers. Rat BMSCs had the earliest proliferative activity by day 7; however, hAFSCs seemed to have the greatest improvement in the regenerative activities. Human ADSCs were the least effective in the terms of proliferative and regenerative activities.
authors: Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. zohoor26203@yahoo.com.
authors: Rehab H
authors: RH
authors: Ashour
authors: Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.|Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Mohamed-Ahdy
authors: MA
authors: Saad
authors: Zoology Unit-Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Mohamed-Ahmed
authors: MA
authors: Sobh
authors: Pathology Department, Mansoura University, Mansoura, Egypt.
authors: Fatma
authors: F
authors: Al-Husseiny
authors: Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Mohamed
authors: M
authors: Abouelkheir
authors: Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Amal
authors: A
authors: Awad
authors: Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Doaa
authors: D
authors: Elghannam
authors: Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Hassan
authors: H
authors: Abdel-Ghaffar
authors: Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, Egypt.|Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Mohamed
authors: M
authors: Sobh
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014183:Transplantation, Heterologous / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D008315:Malondialdehyde; D003404:Creatinine; D013482:Superoxide Dismutase; D005978:Glutathione; D002945:Cisplatin
keywords: Adipose-derived; Amniotic fluid-derived; Cisplatin nephrotoxicity; Mesenchymal stem cells