Effective protection against acute respiratory distress syndrome/ sepsis injury by combined adipose-derived mesenchymal stem cells and preactivated disaggregated platelets

Chih Hung Chen, Yung Lung Chen, Pei Hsun Sung, Cheuk Kwan Sun, Kuan Hung Chen, Yi Ling Chen, Tien Hung Huang, Hung I. Lu, Fan Yen Lee, Jiunn Jye Sheu, Sheng Ying Chung, Mel S. Lee, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

18 Scopus citations

Abstract

This study assessed whether combining adipose-derived mesenchymal stem cells (ADMSC) with preactivated, disaggregated shape-changed platelets (PreD-SCP) was superior to either therapy alone for protecting rat lung from acute respiratory distress syndrome (ARDS) complicated by sepsis. ARDS and sepsis were induced through 100% oxygen inhalation and peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS), respectively. Adult-male Sprague-Dawley rats (n=40) were randomized into sham-control (SC), ARDS-LPS, ARDS-LPS-ADMSC (1.2x106 cells), ARDS-LPS-PreD-SCP (3.0x108, intravenous administration), and ARDS-LPSADMS/ PreD-SCP groups, and were sacrificed 72 h after 48 h ARDS induction. Lung injury scores (LIS) and collagen deposition were highest in ARDS-LPS, lowest in SC, higher in ARDS-LPS+ADMSC than in ARDS-LPS+PreD-SCP and ARDS-LPS+ADMS/ PreD-SCP, and higher in ARDS-LPS+PreD-SCP than in ARDS-LPS+ADMS/PreD-SCP (all p < 0.0001). Alveolar-sac numbers, oxygen saturation, endothelial marker levels, and mitochondrial cytochrome-C levels exhibited opposite patterns with respect to LIS (all p < 0.001). Levels of inflammatory, oxidative-stress, apoptosis, mitochondrial/ DNA damage, and MAPK and Akt signaling markers exhibited patterns identical to that of LIS (all p < 0.001). Anti-oxidant and anti-inflammatory protein levels increased progressively from SC to ARDS-LPS+ADMS/PreD-SCP (all p < 0.0001). These findings indicate combined ADMSC/PreD-SCP was superior to either therapy alone for protecting rat lung from ARDS-sepsis injury.

Original languageEnglish
Pages (from-to)82415-82429
Number of pages15
JournalOncotarget
Volume8
Issue number47
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© Chen et al.

Keywords

  • Acute respiratory distress syndrome
  • Adipose-derived mesenchymal stem cell
  • Inflammation
  • Platelets
  • Sepsis

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