Mesenchymal stem cell using scaffold treatment increased survival on acute liver failure model

Abstract

Background: Recently, the effects of mesenchymal stem cells (MSCs) have been extensively evaluated in acute liver failure model. However, the most commonly used methods are used injecting MSCs through a vessel, which has a major drawback of homing cells in other organs. The aim of current study was to evaluate the efficacy and degree of cell homing of scaffold loaded with MSCs on acute liver failure model. Methods: Acute liver failure was induced in C57BL/6J mice using thioacet-amide (TAA) (200mg/kg, i.p) once a day for 2 days. In phase I, animals were divided in three groups: 1) TAA+saline via tail vein; 2) TAA+MSCs via tail vein; 3) TAA+Scaffold loaded with MSCs to evaluate the mortality and changes in liver function. PLGA Poly (lactic-co-glycolic acid) scaffold alone, and loaded with 1×106 human MSCs were implanted on dorsum of animals. In phase II, animals were divided into three groups: 1) TAA; 2) TAA+Scaffold; 3) TAA+Scaffold loaded with MSCs to evaluate liver function and mortality. Animals were sacrificed 3 days after implantation, serum and liver samples were collected. Liver tissue immunohistochemistry for proliferation marker (Ki67) was performed. Results: In phase I, the mortality rate of TAA+Scaffold group was 36% as compared to TAA+PBS tail vein (66%) and TAA+Scaffold only groups (54%). In phase II, TAA+Scaffold loaded with MSCs group had only 11.8% mortality as compared to TAA (30.4%) and TAA+Sca-fold only (52.6%) (p=0.014) groups. In phase II, serum AST levels of TAA+Scaffold loaded with MSCs was lower than other two groups, while serum ALT levels of TAA+Scaffold group were the lowest. Furthermore, TAA+Scaffold loaded with MSCs group showed increased liver tissue staining for Ki67. Later, we performed PCR using human specific primer, to evaluate homing of MSCs in mouse liver. There was no detection of human cells residing in mouse liver. Conclusion: Scaffold loaded MSCs showed protective effects via paracrine signaling on acute liver failure model. Disclosures: The following authors have nothing to disclose: Yong Kyun Cho, Dae Won Jun, Eun Chul Jang, Seung Min Lee, Joo Hee Kwak