Apr 16, 2020

Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

BioRxiv : the Preprint Server for Biology
J. WuJie Hao

Abstract

Lung injury and fibrosis represent the most significant outcomes of severe and acute lung disorders, including COVID-19. However, there are still no effective drugs to treat lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) manufactured under good manufacturing practice (GMP) requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs through sequentially differentiating hESCs with xeno-free reagents. IMRCs possess a unique gene expression profile distinct from umbilical cord mesenchymal stem cells (UCMSCs), such as higher levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through their paracrine functions. IMRCs are superior to both primary UCMSCs and FDA-approved pirfenidone, with an excellent efficacy and safety profile in mice, monkeys and two severely ill COVID-19 patients in our pilot study. In light of recent public health crises involving pneu...Continue Reading

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Mentioned in this Paper

PLK1 gene
Phosphoric Monoester Hydrolases
DNA Repair
ATM Signaling Pathway
Protein Phosphorylation
PPM1D gene
Human Cell Line
PPM1D wt Allele
Adaptation
CDKN3 protein, human

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