Tags

Type your tag names separated by a space and hit enter

Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with acetaminophen liver injury.
Stem Cell Res 2013; 11(3):1037-44SC

Abstract

OBJECTIVE

Acetaminophen intoxication is a leading cause of acute liver failure. Liver transplantation for acute liver failure is limited by the availability of donor organs. In this study, we aimed at identifying if the transplantation of adipose tissue-mesenchymal stem cells (ASCs) may exert therapeutic effects on acetaminophen-induced liver injury.

METHODS

ASCs were isolated from human subcutaneous tissue and were transfected with a green fluorescent protein (GFP). Sprague-Dawley rats were administrated 300mg/kg of acetaminophen intraperitoneally and were transplanted with ASCs or vehicle. After 24h from acetaminophen administration, rats were sacrificed. Hepatic levels of isoprostanes, 8-hydroxyguanosine (8-OHG), nitrites/nitrates and reduced glutathione (GSH) were determined as markers of oxidative stress; JNK phosphorylation and hepatic levels of inflammatory cytokines and regeneration factors were also assessed.

RESULTS

Transplantation of ASCs decreased AST, ALT and prothrombin time to the levels observed in control rats. Transplanted animals had normal plasma ammonia and did not display clinical encephalopathy. Liver sections of intoxicated rats treated with vehicle showed lobular necrosis and diffuse vacuolar degeneration; in rats transplanted with ASCs liver injury was almost absent. Transplantation of ASCs decreased liver isoprostanes, 8-OHG and nitrite-nitrates to the levels of control rats, while preserving GSH. Consistently, hepatic levels of TNF-α, MCP-1, IL-1β, ICAM-1 and phospho-JNK were markedly increased in rats treated with vehicle and were restored to the levels of controls in animals transplanted with ASCs. Furthermore, ASC transplantation increased liver expression of cyclin D1 and PCNA, two established hepatocyte regeneration factors, whereas ASCs were not able to metabolize acetaminophen in vitro.

CONCLUSION

In this study, we demonstrated that ASC transplantation is effective in treating acetaminophen liver injury by enhancing hepatocyte regeneration and inhibiting liver stress and inflammatory signaling.

Authors+Show Affiliations

U.O.C. di Gastroenterologia, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, Catania, Italy. Electronic address: federicosalomone@rocketmail.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23954692

Citation

Salomone, Federico, et al. "Efficacy of Adipose Tissue-mesenchymal Stem Cell Transplantation in Rats With Acetaminophen Liver Injury." Stem Cell Research, vol. 11, no. 3, 2013, pp. 1037-44.
Salomone F, Barbagallo I, Puzzo L, et al. Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with acetaminophen liver injury. Stem Cell Res. 2013;11(3):1037-44.
Salomone, F., Barbagallo, I., Puzzo, L., Piazza, C., & Li Volti, G. (2013). Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with acetaminophen liver injury. Stem Cell Research, 11(3), pp. 1037-44. doi:10.1016/j.scr.2013.07.003.
Salomone F, et al. Efficacy of Adipose Tissue-mesenchymal Stem Cell Transplantation in Rats With Acetaminophen Liver Injury. Stem Cell Res. 2013;11(3):1037-44. PubMed PMID: 23954692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with acetaminophen liver injury. AU - Salomone,Federico, AU - Barbagallo,Ignazio, AU - Puzzo,Lidia, AU - Piazza,Cateno, AU - Li Volti,Giovanni, Y1 - 2013/07/25/ PY - 2012/10/29/received PY - 2013/07/12/revised PY - 2013/07/16/accepted PY - 2013/8/20/entrez PY - 2013/8/21/pubmed PY - 2014/6/8/medline KW - 8-OHG KW - 8-hydroxyguanosine KW - ALF KW - ASCs KW - BM-MSCs KW - GFP KW - GSH KW - MSCs KW - OLT KW - PCNA KW - acute liver failure KW - adipose tissue mesenchymal stem cells KW - bone marrow mesenchymal stem cells KW - green fluorescent protein KW - mesenchymal stem cells KW - orthotopic liver transplantation KW - proliferating cell nuclear antigen KW - reduced glutathione SP - 1037 EP - 44 JF - Stem cell research JO - Stem Cell Res VL - 11 IS - 3 N2 - OBJECTIVE: Acetaminophen intoxication is a leading cause of acute liver failure. Liver transplantation for acute liver failure is limited by the availability of donor organs. In this study, we aimed at identifying if the transplantation of adipose tissue-mesenchymal stem cells (ASCs) may exert therapeutic effects on acetaminophen-induced liver injury. METHODS: ASCs were isolated from human subcutaneous tissue and were transfected with a green fluorescent protein (GFP). Sprague-Dawley rats were administrated 300mg/kg of acetaminophen intraperitoneally and were transplanted with ASCs or vehicle. After 24h from acetaminophen administration, rats were sacrificed. Hepatic levels of isoprostanes, 8-hydroxyguanosine (8-OHG), nitrites/nitrates and reduced glutathione (GSH) were determined as markers of oxidative stress; JNK phosphorylation and hepatic levels of inflammatory cytokines and regeneration factors were also assessed. RESULTS: Transplantation of ASCs decreased AST, ALT and prothrombin time to the levels observed in control rats. Transplanted animals had normal plasma ammonia and did not display clinical encephalopathy. Liver sections of intoxicated rats treated with vehicle showed lobular necrosis and diffuse vacuolar degeneration; in rats transplanted with ASCs liver injury was almost absent. Transplantation of ASCs decreased liver isoprostanes, 8-OHG and nitrite-nitrates to the levels of control rats, while preserving GSH. Consistently, hepatic levels of TNF-α, MCP-1, IL-1β, ICAM-1 and phospho-JNK were markedly increased in rats treated with vehicle and were restored to the levels of controls in animals transplanted with ASCs. Furthermore, ASC transplantation increased liver expression of cyclin D1 and PCNA, two established hepatocyte regeneration factors, whereas ASCs were not able to metabolize acetaminophen in vitro. CONCLUSION: In this study, we demonstrated that ASC transplantation is effective in treating acetaminophen liver injury by enhancing hepatocyte regeneration and inhibiting liver stress and inflammatory signaling. SN - 1876-7753 UR - https://www.unboundmedicine.com/medline/citation/23954692/Efficacy_of_adipose_tissue_mesenchymal_stem_cell_transplantation_in_rats_with_acetaminophen_liver_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1873-5061(13)00085-8 DB - PRIME DP - Unbound Medicine ER -