Impact of MSCs against Hepatic I/R Injury Figure 4. Minimal TUNEL-positive hepatocytes by BM-MSC transplantation. TUNEL staining of I/R-injured liver sections from the MSC group (A. upper panel) and the Control group (B. lower panel). C. Quantification of TUNEL-positive hepatocyte nuclei was assessed by calculating the mean of the number of TUNEL-positive hepatocytes in 10 random high-power fields per animal. Abbreviations: CV, central vein; PV, portal vein. doi:10.1371/journal.pone.0019195.g004 To examine the recovery of the remnant liver, we assessed the liver regeneration rate. As shown in Figure 7, the liver regeneration rate in the MSC group was significantly increased 168 h after reperfusion compared with the Control group (P,0.03). Discussion BM-MSCs have the capacity for self-renewal and multipotency, and can differentiate into bone, fat and cartilage cells [9,10]. Cell- based therapy has recently been considered a prominent tool in regenerative medicine. However, the use of embryonic stem cells or induced pluripotent stem cells is ethically controversial and can also result in teratoma formations that hinder the applications of stem cell therapy. One way to circumvent these issues is to use MSCs, as they are an attractive alternative for regenerative medicine. In recent years, MSC transplantation has been broadly used in animal models of cerebral infarction, myocardial infarction, and renal I/R injury to regenerate damaged tissues. Some reports have published the effectiveness of MSC transplantation against drug- induced liver injury [4,5]. However, the effectiveness of MSC transplantation against hepatic I/R injury remains unknown. Hepatic I/R injury results in pathological changes such as congestion, vacuolization, and apoptosis in liver tissue, which can lead to hepatic failure. Figure 5. LacZ-positive BM-MSCs distributed around the periportal area. Photomicrograph of liver sections stained with X-gal from a rat 6 h after reflow. A. LacZ-positive MSCs (blue) detected around the periportal area. B. MSCs detected in the sinusoid (right panel). doi:10.1371/journal.pone.0019195.g005 PLoS ONE | www.plosone.org 4 April 2011 | Volume 6 | Issue 4 | e19195