Research Papers:
Effective protection against acute respiratory distress syndrome/sepsis injury by combined adipose-derived mesenchymal stem cells and preactivated disaggregated platelets
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Abstract
Chih-Hung Chen1, Yung-Lung Chen2, Pei-Hsun Sung2, Cheuk-Kwan Sun3, Kuan-Hung Chen4, Yi-Ling Chen2, Tien-Hung Huang2, Hung-I Lu5, Fan-Yen Lee5, Jiunn-Jye Sheu5, Sheng-Ying Chung2, Mel S. Lee6,* and Hon-Kan Yip2,7,8,9,10,*
1Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
2Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
3Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Kaohsiung, Taiwan
4Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
5Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
6Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
7Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
8Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
9Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
10Department of Nursing, Asia University, Taichung, Taiwan
*Both authors contributed equally to this work
Correspondence to:
Hon-Kan Yip, email: [email protected]
Mel S. Lee, email: [email protected]
Keywords: acute respiratory distress syndrome, sepsis, inflammation, adipose-derived mesenchymal stem cell, platelets
Received: October 11, 2016 Accepted: March 06, 2017 Published: July 17, 2017
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-LPS-ADMS/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.
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