Equal distribution of mesenchymal stem cells after hepatic ischemia–reperfusion injury

Abstract

BackgroundLiver ischemia–reperfusion (I/R) injury is one of the major causes of hepatocellular injury-related mortality and morbidity after liver transplantation. Mesenchymal stem cells (MSCs) have been shown to reduce liver I/R injury and improve regeneration. The purpose of the present study was to investigate the difference in the distribution of systemically delivered MSCs in the recipient's liver between the ischemic injury area and nonischemic area. Material and methodsFishers' rats (7-8 week of age) were used as donors of MSCs and recipients. Bone marrow-derived MSCs were isolated from the donor's femur. Before systemic administration, MSCs were labeled with the fluorescent dye PKH26. The rats were divided into four groups: (1) I/R injury + MSC group, (2) MSC only, without I/R injury, (3) I/R injury + saline group, and (4) the Sham group. I/R injury was performed by clamping the inflow vascular structures of the left and middle lobes of the recipient's liver for 60 min. The right lobe was considered as a nonischemic part. Subsequently, 1.5 × 106 of MSCs or saline (NaCl, 0.9%) was administrated via the rat's tail vein. Thereafter, the rats were killed after days one, three, or seven for the analyses. ResultsA fluorescent microscopy assay for labeled MSCs showed positive cells in both ischemic and nonischemic parts of the recipient's liver. The number of cells was significantly higher in the I/R injury + MSC group compared with the only MSC, without I/R injury group. Immunohistochemical staining showed that there was no significant difference in the proliferation of Ki-67-positive cells between the I/R + MSCs and I/R + saline groups. In addition, the serum transaminase levels were not different between the I/R + MSCs and I/R + saline groups. ConclusionsAfter partial liver I/R injury, transplanted MSCs migrate equally to the ischemic and nonischemic parts of the recipient's liver. Considering the unique ability of the liver to regenerate, both parts of the liver presumably receive signals for regeneration.