급성 간부전 모델에서 지지체를 이용한 줄기세포의 치료 효과

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 thioacetamide (TAA) (200mg/kg, i.p) once a day for 2 days. Animals were divided in four groups: 1) TAA; 2) TAA+Scaffold without MSCs; 3) TAA+MSC injected through tail vein; 4) TAA+Scaffold loaded with MSCs to evaluate the mortality and changes in liver function. Poly(lactic-co-glycolic acid) (PLGA) scaffold alone, and loaded with 1x106 human MSCs were implanted on dorsum of animals. Animals were sacrificed 4 days after implantation, serum and liver samples were collected. Liver tissue immunohistochemistry for proliferation marker (Ki67), for hepatocyte marker (CYP2E1) were performed. Stem cell homing in mouse liver was evaluated with PCR, immunohistochemistry for human specific marker. Results: TAA+Scaffold loaded with MSCs group had only 31.4% mortality as compared to TAA (55.9%) (p=0.013), MSC tail vein (41.2%), and TAA+Scafold only (63.2%) (p=0.027) groups. 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. In scaffold loaded with MSC, positive stain was found using CYP2E1, liver specific marker. Conclusion: Scaffold loaded MSCs showed protective effects via paracrine signaling on acute liver failure model.