Spheroid-cultured human umbilical cord-derived mesenchymal stem cells attenuate hepatic ischemia-reperfusion injury in rats.

Abstract

Mesenchymal stem cell (MSC) transplantation is a promising treatment for ischemia-reperfusion injury (IRI). However, its effects on hepatic IRI were not consistent in the previous studies. 3D spheroid-cultured MSCs enhance their production of trophic and anti-inflammatory properties, but their effects on hepatic IRI remain unclear. In this study, we compared the 3D spheroid-cultured human umbilical derived MSCs (3D UC-MSCs) with 2D-cultured UC-MSCs (2D UC-MSCs) on treating hepatic IRI. The RNA sequencing data showed that suppression of cell mitosis, response to hypoxia, inflammation, and angiogenesis were the top genetic changes in 3D UC-MSCs compared with 2D UC-MSCs. Although both pro-inflammatory and anti-inflammatory genes were upregulated in the 3D UC-MSCs, the mRNA and protein of an RNase (ZC3H12A), which turnovers the mRNA of pro-inflammatory genes at the post-transcript level, were significantly upregulated in 3D UC-MSCs. 3D UC-MSCs reduced the secretion of many chemokines and growth factors, but increased the secretion of vascular endothelial growth factor. Compared with the vehicle and 2D UC-MSCs, 3D UC-MSCs significantly reduced hepatic IRI in rats, based on the plasma aminotransferase levels, liver damage scores, neutrophil infiltration, hepatocyte apoptosis and expression of inflammation-associated genes. These findings suggest that 3D UC-MSCs therapy is a promising treatment for hepatic IRI.

• Authors: Yi Sun, Yang Wang, Liang Zhou, Yizhou Zou, Gengwen Huang, Ge Gao, Shi Ting, Xiong Lei, Xiang Ding
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 2518 (02 06 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29410537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines

Topics

• Animals
• Apoptosis
• Chemokines (metabolism)
• Disease Models, Animal
• Humans
• Inflammation (metabolism)
• Liver (blood supply)
• Liver Diseases (therapy)
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells (cytology)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (therapy)
• Spheroids, Cellular
• Umbilical Cord (cytology)