# Optimizing the Infusion Route of Human Bone Marrow Mesenchymal Stromal Cells to Mitigate Liver Ischemia–Reperfusion Injury in a Porcine Model

## TL;DR

This study shows that delivering human bone marrow cells through the hepatic artery is a safe and effective way to protect the liver from injury in a pig model.

## Contribution

The study identifies the hepatic artery as the optimal route for cell delivery to achieve uniform liver distribution and biological effects.

## Key findings

- BM-MSC infusion did not obstruct hepatic or pulmonary blood flow within 6 hours.
- Arterial infusion resulted in higher BM-MSC retention in the left liver lobe compared to portal infusion.
- BM-MSCs prevented gene expression changes related to inflammation and energy metabolism in the liver.

## Abstract

Mesenchymal stromal cells (MSC) have been shown to mitigate IRI through their anti-inflammatory and immune-modulating capacities. This study aims to demonstrate the feasibility, safety, and effectiveness of hepatic administration of bone marrow-derived (BM)-MSCs in a large pig model relevant to human anatomy. After complete vascular exclusion for 45 min, 3 × 106 human BM-MSCs/kg body weight were infused via the portal vein or hepatic artery. BM-MSC infusion did not cause obstruction of hepatic or pulmonary blood flow within 6 h after infusion. Cells were effectively retained in the liver, being undetectable in peripheral blood, lung, and spleen samples. Human B2M expression, as a marker for BM-MSC presence, was significantly higher for the left liver lobe in arterial infusion compared to portal infusion. In liver samples with high BM-MSC levels, we identified the prevention of up- or downregulation of some genes related to inflammation and energy metabolism that was present in non-treated control samples, indicating biological effects within 6 h of infusion. We conclude that hepatic BM-MSC infusion is feasible and safe, with the hepatic artery serving as the optimal administration route for homogenous distribution. These findings pave the way for clinical studies on MSC infusion in IRI, either in situ in liver conditions or ex situ during machine perfusion.