Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis.
Cell Res
; 30(9): 794-809, 2020 09.
Article
in English
| MEDLINE | ID: covidwho-601806
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) produced under good manufacturing practice requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from that of umbilical cord mesenchymal stem cells (UCMSCs), such as higher expression 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 paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and the FDA-approved drug pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute lung injury and acute respiratory distress syndrome, our findings suggest that IMRCs are ready for clinical trials on lung disorders.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Mesenchymal Stem Cell Transplantation
/
Lung Injury
/
Mesenchymal Stem Cells
/
Human Embryonic Stem Cells
/
Lung
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Cell Res
Year:
2020
Document Type:
Article
Affiliation country:
S41422-020-0354-1
Similar
MEDLINE
...
LILACS
LIS