Evaluation of different routes of administration and biodistribution of human amnion epithelial cells in mice

Abstract

Placenta is a non-controversial and promising source of cells for the treatment of several liver diseases. We previously reported that transplanted human amnion epithelial cells (hAECs) differentiate into hepatocyte-like cells, resulting in correction of mouse models of metabolic liver disease or acute hepatic failure. As part of preclinical safety studies, we investigated the distribution of hAECs using two routes of administration to efficiently deliver hAECs to the liver. Optical imaging is commonly used because it can provide fast, high-throughput, whole-body imaging, thus DiR-labeled hAECs were injected into immunodeficient mice, via the spleen or the tail vein. The cell distribution was monitored using an in vivo imaging system over the next 24 h. After splenic injection, the DiR signal was detected in liver and spleen at 1, 3 and 24 h post-transplant. The distribution was confirmed by analysis of human DNA content at 24 h post-transplant and human-specific cytokeratin 8/18 staining. Tail vein infusion resulted in cell engraftment mainly in the lungs, with minimal detection in the liver. Delivery of cells to the portal vein, via the spleen, resulted in efficient delivery of hAECs to the liver, with minimal, off-target distribution to lungs or other organs.