Regenerative Effect of Bone Marrow-derived Mesenchymal Stem Cells in Thioacetamide-induced Liver Fibrosis of Rats

Document Type: Original Articles

Authors

1 Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Burn and Wound Healing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Comparative and Experimental Medicine Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

5 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

6 PhD in Veterinary Reproduction, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

7 Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

8 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

9 Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

The present study determined the regenerative effect of bone marrow-derived stem cells (BMSCs) on thioacetamide (TA)-induced liver fibrosis in rats. A total of 30 male Wistar rats were randomly divided into sham control and treatment groups. The rats of the sham control group were subdivided into three groups and sampled on the 14th, 18th, and 20th weeks after fibrosis induction. The rats of the treatment group were subdivided into two groups and sampled on the 4th and 6th weeks after BMSCs treatment. Fibrosis was induced by the intraperitoneal administration of 200 mg/kg of TA twice a week for a period of 14 weeks. All the animals underwent liver function tests and histopathologic evaluation 4 and 6 weeks after BMSCs transplantation. The BMSCs were characterized using osteogenic induction and reverse transcription-polymerase chain reaction. The BMSCs were plastic adherent, spindle-shaped, and positive for osteogenic differentiation. They expressed CD73 and were negative for CD45. The infiltration of inflammatory cells and deposition of collagen fibers were noticed after TA administration. A significant decline in inflammatory cells and a healing process were detected 4 weeks after cell transplantation. The amelioration in hepatic tissue was significant 6 weeks after cell therapy. Following the injection of BMSCs, a nonsignificant decrease was visible in aspartate transaminase level; however, this decline was significant for alanine aminotransferase level. The alkaline phosphatase and albumin levels showed an increasing trend after cell administration. The transplantation of BMSCs resulted in a significant regenerative effect after hepatic injuries. Therefore, it was shown that BMSCs transplantation can open a new window and be a therapy of choice in the amelioration of liver fibrosis.

Keywords

Main Subjects


Article Title [French]

Effet Régénérateur des Cellules Souches Mésenchymateuses Dérivées de la Moelle Osseuse dans la Fibrose Hépatique Induite par le Thioacétamide

Abstract [French]

La présente étude a permis de déterminer l’effet régénérateur des cellules souches dérivées de la moelle osseuse (BMSCs) sur la fibrose hépatique induite par le thioacétamide (TA) chez les rats. Au total, 30 rats Wistar mâles ont été répartis au hasard en groupes témoin et traitement. Les rats du groupe témoin fictif ont été subdivisés en trois groupes et échantillonnés 14, 18 et 20 semaines après l'induction de la fibrose. Les rats du groupe de traitement ont été subdivisés en deux groupes et échantillonnés aux quatrième et sixième semaines après le traitement par BMSCs. La fibrose a été provoquée par l'administration intrapéritonéale de 200 mg / kg d'AT deux fois par semaine pendant 14 semaines. Tous les animaux ont subi des tests de la fonction hépatique et une évaluation histopathologique 4 et 6 semaines après la transplantation de BMSC. Les BMSC ont été caractérisées par induction ostéogénique et transcription inverse, réaction en chaîne avec une polymérase. Les BMSC étaient plastiques adhérents, en forme de fuseau et positives pour la différenciation ostéogénique. Ils ont exprimé CD73 et étaient négatifs pour CD45. L'infiltration de cellules inflammatoires et le dépôt de fibres de collagène ont été remarqués après l'administration de TA. Une diminution significative des cellules inflammatoires et un processus de guérison ont été détectés 4 semaines après la transplantation de cellules. L'amélioration du tissu hépatique était significative 6 semaines après la thérapie cellulaire. Après l’injection de BMSC, une diminution non significative du niveau d’aspartate transaminase a été observée; Cependant, cette diminution était significative pour le niveau d'alanine aminotransférase. Les taux de phosphatase alcaline et d’albumine ont montré une tendance à la hausse après l’administration de cellules. La transplantation de BMSC a entraîné un effet régénérateur important après une lésion hépatique. Par conséquent, il a été démontré que la transplantation de BMSC peut ouvrir une nouvelle fenêtre et constituer un traitement de choix dans l’amélioration de la fibrose hépatique.

Keywords [French]

  • Moelle Osseuse
  • Cellule Souche Mésenchymateuse
  • Foie
  • Thioacétamide
  • Fibrose
  • rat
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