Abstract
Clinical hepatocyte transplantation (HTx) is only performed without general anesthesia, while inhalation anesthetics are usually used in animal experiments. We hypothesized that isoflurane may be a possible reason for the discrepancy between the results of animal experiments and the clinical outcomes of HTx. Syngeneic rat hepatocytes (1.0 × 107) were transplanted to analbuminemic rats with (ISO group) and without (AW group) isoflurane. The serum albumin, AST, ALT, LDH levels and several inflammatory mediators were analyzed. Immunohistochemical staining and ex vivo imaging were also performed. The serum albumin levels of the ISO group were significantly higher in comparison to the AW group (p < 0.05). The serum AST, ALT, LDH levels of the ISO group were significantly suppressed in comparison to the AW group (p < 0.0001, respectively). The serum IL-1β, IL-10, IL-18, MCP-1, RNTES, Fractalkine and LIX levels were significantly suppressed in the ISO group. The ischemic regions of the recipient livers in the ISO group tended to be smaller than the AW group; however, the distribution of transplanted hepatocytes in the liver parenchyma was comparable between the two groups. Isoflurane may at least in part be a reason for the discrepancy between the results of animal experiments and the clinical outcomes of HTx.
Highlights
Clinical hepatocyte transplantation (HTx) is only performed without general anesthesia, while inhalation anesthetics are usually used in animal experiments
In the AW group, the serum albumin levels appeared to plateau at 28 days after hepatocyte transplantation
Given that clinical hepatocyte transplantation is only performed without general anesthesia—unlike animal experiments in which it is only performed under general anesthesia—the large discrepancy between the results of animal experiments and the clinical outcomes of hepatocyte transplantation may logically be explained by the use of isoflurane
Summary
Clinical hepatocyte transplantation (HTx) is only performed without general anesthesia, while inhalation anesthetics are usually used in animal experiments. We hypothesized that isoflurane may be a possible reason for the discrepancy between the results of animal experiments and the clinical outcomes of HTx. Syngeneic rat hepatocytes (1.0 × 1 07) were transplanted to analbuminemic rats with (ISO group) and without (AW group) isoflurane. The serum AST, ALT, LDH levels of the ISO group were significantly suppressed in comparison to the AW group (p < 0.0001, respectively). Hepatocyte transplantation is obviously associated with many hurdles, including hepatocyte isolation[12], graft preservation[13], graft quality evaluation[14], and hepatocyte e ngraftment[15,16] Among these factors, the extremely poor engraftment of hepatocytes is a highpriority issue that must be overcome. Slehria et al previously reported that the use of vasodilators dramatically increased the entry of transplanted hepatocytes into the recipient’s liver tissues, and improved hepatocyte e ngraftment[29]
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