Purpose: Whole liver transplantation, an effective therapy for many inherited and acquired hepatic disorders, has limitations including donor shortage and fatal surgical complications. Hepatocyte transplantation, which is simpler and less
expensive than whole liver transplantation, allows the use of living related donors, permits the use of a single donor organ for multiple recipients, and makes possible the cryopreservation of hepatocytes for future use. However, choosing a
proper
scaffold for hepatocytes hampers wide use of hepatocyte transplantation. We performed hepatocyte transplantation using biodegradable injectable polymers, fabricated form poly (lactide-co-glycolide) (PLGA) microspheres, as scaffolds to evaluate
their
effectiveness.
Methods: Female, five week old FVB mice, were prepared for donors, and four male, five week old nude mice, were used for recipients. Liver cells were isolated from FVB donors. The cell viability exceeded 95% as assessed by trypan blue
exclusion
method. For three nude mice, 2×106 cells resuspended in 200 ㎕ medium were mixed with 200 ㎕ PLGA microspheres, and were injected into the peritoneal cavity of each mouse. One nude mouse was transplanted with 2×106 cells
resuspended in 200 ㎕ medium only, and it served as a negative control. Specimens were retrieved at one week, and histological and immunohistochemical analyses were performed.
Results: In the negative control, all transplanted hepatocytes disappeared at one week. In mice transplanted both microspheres and hepatocytes, conglomerates, which contained hepatocytes, were observed in the peritoneal cavity, The
hepatocytes
were identified by H & E staining and immunohistochemistry using anti-hepatocyte antibody.
Conclusion: In this preliminary study, stable hepatocyte engraftment was achieved in hepatocyte transplantation with PLGA microspheres, but not in hepatocyte transplantation only. More studies on comparison between sponge-type scaffolds
and
injectable scaffolds would be necessary. Improvement on both initial vascularization and proliferation of transplanted hepatocytes is a target of our future work.
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