Early and Dose-Dependent Xenogeneic Mesenchymal Stem Cell Therapy Improved Outcomes in Acute Respiratory Distress Syndrome Rodent Through Ameliorating Inflammation, Oxidative Stress, and Immune Reaction

Kun Chen Lin, Wen Feng Fang, Pei Hsun Sung, Kuo Tung Huang, John Y. Chiang, Yi Ling Chen, Chi Ruei Huang, Yi Chen Li, Mel S. Lee, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations

Abstract

This study tested whether human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) treatment effectively protected the rat lung against acute respiratory distress syndrome (ARDS) injury, and benefits of early and dose-dependent treatment. Rat pulmonary epithelial cell line L2 (PECL2) were categorized into G1 (PECL2), G2 (PECL2 + healthy rat lung-derived extraction/50 mg/ml co-cultured for 24 h), G3 (PECL2 + ARDS rat lung-derived extraction/50 mg/ml co-cultured for 24 h), and G4 (condition as G3 + HUCDMSCs/1 × 10 5/co-cultured for 24 h). The result showed that the protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IkB/NF-κB/IL-1β/TNF-α), oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/JNKs/JUN/cytosolic-cytochrome-C/cyclophilin-D/DRP1), and cell-apoptotic/fibrotic (cleaved-caspase 3/cleaved-PARP/TGF-β/p-Smad3) biomarkers were significantly increased in G3 than in G1/G2 and were significantly reversed in G4 (all P < 0.001), but they were similar between G1/G2. Adult male rats ( n = 42) were equally categorized into group 1 (normal control), group 2 (ARDS only), group 3 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 3 h after 48 h ARDS induction (i.e., early treatment)], group 4 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 24 h after 48 h ARDS induction (late treatment)], and group 5 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 3 h/24 h after-48 h ARDS induction (dose-dependent treatment)]. By day 5 after ARDS induction, the SaO 2%/immune regulatory T cells were highest in group 1, lowest in group 2, significantly lower in group 4 than in groups 3/5, and significantly lower in group 3 than in group 5, whereas the circulatory/bronchioalveolar lavage fluid inflammatory cells (CD11b-c+/LyG6+/MPO+)/circulatory immune cells (CD3-C4+/CD3-CD8+)/lung-leakage-albumin level/lung injury score/lung protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IκB-β/p-NF-κB/IL-1β/TNF-α)/fibrotic (p-SMad3/TGF-β), apoptosis (mitochondrial-Bax/cleaved-caspase-3)/oxidative-cell-stress (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/p-JNKs/p-cJUN)/mitochondrial damaged (cyclophilin-D/DRP1/cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of SaO 2% among the groups (all P < 0.0001). Early administration was superior to and two-dose counterpart was even more superior to late HUCDMSCs treatment for protecting the lung against ARDS injury.

Original languageEnglish
Pages (from-to)9636897231190178
JournalCell Transplantation
Volume32
DOIs
StatePublished - 01 01 2023

Bibliographical note

Publisher Copyright:
© The Author(s) 2023.

Keywords

  • acute respiratory distress syndrome
  • immune cells
  • inflammation
  • oxidative stress
  • xenogeneic mesenchymal stem cells
  • Respiratory Distress Syndrome/therapy
  • Oxidative Stress
  • Transforming Growth Factor beta/metabolism
  • Humans
  • Male
  • Cyclophilins/metabolism
  • Tumor Necrosis Factor-alpha/metabolism
  • Cytochromes/metabolism
  • Toll-Like Receptor 2/metabolism
  • TNF Receptor-Associated Factor 6/metabolism
  • Inflammation/therapy
  • Rats
  • Myeloid Differentiation Factor 88/metabolism
  • Mesenchymal Stem Cells/metabolism
  • Biomarkers/metabolism
  • HMGB Proteins/metabolism
  • Rats, Sprague-Dawley
  • Animals
  • Toll-Like Receptor 4/metabolism
  • NF-kappa B/metabolism
  • Rodentia/metabolism
  • Adaptor Proteins, Vesicular Transport/metabolism
  • Mesenchymal Stem Cell Transplantation

Fingerprint

Dive into the research topics of 'Early and Dose-Dependent Xenogeneic Mesenchymal Stem Cell Therapy Improved Outcomes in Acute Respiratory Distress Syndrome Rodent Through Ameliorating Inflammation, Oxidative Stress, and Immune Reaction'. Together they form a unique fingerprint.

Cite this