There was no evidence of hepatocyte regeneration in any of the specimens. In contrast, new lobules were regenerated in the surviving animals of the IPT group at week 2 after intraportal hBMSC transplantation. Microthrombosis in the sinusoids and other types of microvascular liver necrosis were not observed in the recipient animal livers. After 3 weeks, the surviving animals showed approximately normal liver structures, and no deviations from the normal liver structure were observed selleck inhibitor at week 5. These data were confirmed by biochemistry.

Transfused hBMSCs were detected by immunohistochemistry with the anti-human hepatocyte-specific antibodies ALB and HSA. The IPT group showed hBMSC-derived hepatocytes in the animal liver tissue. Immunohistochemistry of the serial sections revealed that hBMSC-derived hepatocytes that were positive for ALB and HSA were widely distributed in the hepatic lobule at weeks 2, 5, and 10 after IPT (Fig. 5). Approximately 30% of the cells were double-positive cells, and these cells appeared in hepatic lobules as a mass, as small clusters, and as scattered individual cells. This finding indicates that the transplanted hBMSCs were well-integrated in the liver

parenchyma. However, the number of transplanted hBMSC-derived hepatocytes was significantly decreased at week 15, and only a few single cells were scattered in the regenerated liver lobules at week 20 (Fig. 6). Thus, the present data demonstrate the capability of adult human BMSCs to differentiate into this website hepatocytes 上海皓元 and repopulate the liver in FHF. The ELISA results (Fig. 7A) show that the concentration of human ALB in the animals reached

2.02 ± 0.35 g/L at week 2 and increased to 3.88 ± 0.95 g/L and 3.92 ± 0.55 g/L at weeks 5 and 10, respectively. The level of human ALB subsequently decreased to 1.23 ± 0.3 g/L at week 15 and 0.87 ± 0.29 g/L at week 20. The results of qPCR (Fig. 7B) indicate that human hepatocyte-specific genes (ALB, CK8, G6PD, and HNF-1α) were expressed at week 2 after hBMSC IPT. Progressive increases in the expression of these genes were observed within 10 weeks after hBMSC IPT. After 15 weeks, the expression of these genes decreased gradually. Except for a very low level of G6PD transcripts, the expression of these genes was not detectable at week 20. The surviving animals that received hBMSCs via IPT showed no evidence of tumors in the liver during a preliminary tumorigenicity assay at 6 months after transplantation. No tumors were detected in other organs (including the brain, heart, lung, kidney, spleen, and pancreas) by H&E staining. Several nonrandomized clinical trials have demonstrated the safety and promising beneficial effects of hBMSCs in the treatment of liver cirrhosis,14, 15 although the long-term chronic hepatic failure caused by hepatitis B was not markedly improved.