ABSTRACT
BACKGROUND: Mesenchymal stem cells (MSCs) migrate and transmigrate to acute liver failure (ALF) area due to vascular endothelial growth factor (VEGF) stimulation as an attractant molecule then actively giving the paracrine signaling and or differentiating into primary hepatocytes, however the best route of MSCs transplanted to liver injury area remains unclear. AIM: In this study we compare intravenous (IV) and intraperitoneal (IP) route of MSCs administration by analyzing serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin level as improvement markers of liver function and VEGF as attractant-proliferation molecule on days 2 and 5. MATERIALS AND METHODS: Eighteen male Sprague-Dawley rats weighting 200 g were used in this study. They were divided in three study groups: vehicle control, IP and IV groups. The IV group was treated by MSCs at dose 1×106 by lateral tail vein injection and IP group received 1×106 MSCs via IP injection. The level of SGPT, SGOT and bilirubin were measured by an automatic analyzer, the VEGF level using enzyme-linked immunosorbent assay (ELISA), while the CD73 expression was evaluated using immunohistochemistry. RESULTS: This study showed that IV injection of MSCs was more efficient for increasing liver function than IP treatment group that confirmed by the observed significant decrease in SGPT, SGOT and bilirubin level on days 2 and 5 (p<0.001). This effect was most likely mediated by the significant increase of VEGF level (p<0.05) on days 2 and 5. CONCLUSION: Our result conclude that an IV administration of MSCs was more efficacious than the IP administration for liver injury regeneration.
Subject(s)
Liver Failure, Acute/blood , Liver/pathology , Mesenchymal Stem Cell Transplantation/methods , 5'-Nucleotidase/blood , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Bilirubin/blood , Carbon Tetrachloride/toxicity , Disease Models, Animal , Injections, Intraperitoneal , Injections, Intravenous , Liver Failure, Acute/chemically induced , Liver Failure, Acute/pathology , Liver Regeneration , Male , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/bloodABSTRACT
BACKGROUND: Mesenchymal stem cells (MSCs) may serve as immunoregulators by producing various anti-inflammatory molecules. Under sufficient level of TNF-α, MSCs become activated and adopt immune-suppressive phenotype (MSCs type-2) by releasing various anti-inflammatory molecule including TGF-ß and IL-10. However, the ability of MSC itself to produce IL-10 under TNF-α stimulation and the correlation of TGF-ß production of MSCs to IL-10 level remains to be elucidated. AIM: In this study, MSCs were activated with various TNF-α doses to determine the increase of IL-10 and TGF-ß level as well as its correlation. MATERIAL AND METHODS: This study used post-test only control group design, by using 3 study groups, consist of 1 control (C) and 2 treatments (T) (TNF-α = 5 and 10 ng/mL) with triplicate induced in MSC for 24 hours, then the levels of IL-10 and TGF-ß were measured by using ELISA assay. RESULTS: The results of this study showed a significant increase of TGF-ß and IL-10 levels (p < 0.05) at TNF-α 5 and 10 ng/mL dose of TNF-α. Moreover, there was a significant negative correlation between TGF-ß and IL-10 level on 5 and 10 ng/mL dose TNF-α treatment. CONCLUSION: Based on our study, we conclude that the 5 ng/mL dose of TNF-α is a sufficient dose for MSCs to suppress the inflammatory milieu. The higher increase of TGF beta is due to the controlled inflammation by IL-10.
