# Comparison of the Efficacy of Two Routes of Administration of Human Amniotic Epithelial Cells in Cell Therapy of Acute Hepatic Insufficiency

## TL;DR

This study compares how two different ways of giving human amniotic cells affect their ability to treat severe liver damage in mice.

## Contribution

It shows that intravenous delivery leads to more effective liver repair than intraperitoneal delivery.

## Key findings

- Intravenously administered cells mostly accumulated in the lungs but still helped repair the liver.
- Intraperitoneally administered cells mainly reached the liver but had limited regenerative effects.
- Cell engraftment efficiency varied significantly between the two administration routes.

## Abstract

The route of administration of implanted cells may affect the outcome of cell therapy by directing cell migration to the damaged site. However, the question of the relationship between the route of administration, the efficacy of colonisation of a given organ, and the efficacy of cell therapy has not been resolved. The aim of the study was to localise transplanted intravenously and intraperitoneally human amniotic epithelial cells (hAECs) in the tissues of mice, both healthy and injured, in an animal experimental model of acute liver failure (ALF). Mice intoxicated with D-Galactosamine (D-GalN) at a dose of 150 mg/100 g body weight received D-GalN alone or with a single dose of hAECs administered by different routes. Subsequently, at 6, 24, and 72 h after D-GaIN administration and at 3, 21, and 69 h after hAEC administration, lungs, spleen, liver, and blood were collected from recipient mice. The degree of liver damage and regeneration was assessed based on biochemical blood parameters, histopathological evaluation (H&E staining), and immunodetection of proliferating (Ki67+) and apoptotic (Casp+) cells. The biodistribution of the administered cells was based on immunohistochemistry and the identification of human DNA. It has been shown that after intravenous administration, in both healthy and intoxicated mice, most of the transplanted hAECs were found in the lungs, while after intraperitoneal administration, they were found in the liver. We concluded that a large number of hAECs implanted in the lungs following intravenous administration can exert a therapeutic effect on the damaged liver, while the regenerative effect of intraperitoneally injected hAECs on the liver was very limited due to the relatively lower efficiency of cell engraftment.