PMID- 36012176
OWN - NLM
STAT- MEDLINE
DCOM- 20220829
LR  - 20230308
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 16
DP  - 2022 Aug 10
TI  - Reduction of Emphysema Severity by Human Umbilical Cord-Derived Mesenchymal Stem 
      Cells in Mice.
LID - 10.3390/ijms23168906 [doi]
LID - 8906
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and 
      mortality in chronic lung disease patients throughout the world. Mesenchymal stem 
      cells (MSCs) have been shown to regulate immunomodulatory, anti-inflammatory, and 
      regenerative responses. However, the effects of human-umbilical-cord-derived 
      mesenchymal stem cells (hUC-MSCs) on the lung pathophysiology of COPD remain 
      unclear. We aimed to investigate the role of hUC-MSCs in emphysema severity and 
      Yes-associated protein (Yap) phosphorylation (p-Yap) in a 
      porcine-pancreatic-elastase (PPE)-induced emphysema model. We observed that the 
      emphysema percentages (normalized to the total lung volume) measured by chest 
      computed tomography (CT) and exercise oxygen desaturation were significantly 
      reduced by hUC-MSCs at 107 cells/kg body weight (BW) via intravenous 
      administration in emphysematous mice (p < 0.05). Consistently, the emphysema 
      index, as assessed by the mean linear intercept (MLI), significantly decreased 
      with hUC-MSC administration at 3 x 106 and 107 cells/kg BW (p < 0.05). Changes in 
      the lymphocytes, monocytes, and splenic cluster of differentiation 4-positive 
      (CD4+) lymphocytes by PPE were significantly reversed by hUC-MSC administration 
      in emphysematous mice (p < 0.05). An increasing neutrophil/lymphocyte ratio was 
      reduced by hUC-MSCs at 3 x 106 and 107 cells/kg BW (p < 0.05). The higher levels 
      of tumor necrosis factor (TNF)-alpha, keratinocyte chemoattractant (KC), and lactate 
      dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) were significantly 
      decreased by hUC-MSC administration (p < 0.05). A decreasing p-Yap/Yap ratio in 
      type II alveolar epithelial cells (AECII) of mice with PPE-induced emphysema was 
      significantly increased by hUC-MSCs (p < 0.05). In conclusion, the administration 
      of hUC-MSCs improved multiple pathophysiological features of mice with 
      PPE-induced emphysema. The effectiveness of the treatment of pulmonary emphysema 
      with hUC-MSCs provides an essential and significant foundation for future 
      clinical studies of MSCs in COPD patients.
FAU - Laiman, Vincent
AU  - Laiman V
AD  - International Ph.D. Program in Medicine, College of Medicine, Taipei Medical 
      University, Taipei 110, Taiwan.
AD  - Department of Anatomical Pathology, Faculty of Medicine, Public Health and 
      Nursing, Universitas Gadjah Mada-Dr. Sardjito Hospital, Yogyakarta 55281, 
      Indonesia.
FAU - Lee, Yueh-Lun
AU  - Lee YL
AD  - Department of Microbiology and Immunology, School of Medicine, College of 
      Medicine, Taipei Medical University, Taipei 110, Taiwan.
FAU - Hou, Yu-Wei
AU  - Hou YW
AD  - School of Respiratory Therapy, College of Medicine, Taipei Medical University, 
      Taipei 110, Taiwan.
FAU - Fang, Yu-Ting
AU  - Fang YT
AD  - Department of Biomedical Engineering, National Yang Ming Chiao Tung University, 
      Taipei 112, Taiwan.
FAU - Chen, You-Yin
AU  - Chen YY
AUID- ORCID: 0000-0003-4869-3857
AD  - Department of Biomedical Engineering, National Yang Ming Chiao Tung University, 
      Taipei 112, Taiwan.
FAU - Lo, Yu-Chun
AU  - Lo YC
AD  - Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and 
      Technology, Taipei Medical University, Taipei 110, Taiwan.
FAU - Heriyanto, Didik Setyo
AU  - Heriyanto DS
AD  - Department of Anatomical Pathology, Faculty of Medicine, Public Health and 
      Nursing, Universitas Gadjah Mada-Dr. Sardjito Hospital, Yogyakarta 55281, 
      Indonesia.
FAU - Lan, Shu-Chi
AU  - Lan SC
AD  - School of Respiratory Therapy, College of Medicine, Taipei Medical University, 
      Taipei 110, Taiwan.
FAU - Chen, Chia-Ling
AU  - Chen CL
AD  - School of Respiratory Therapy, College of Medicine, Taipei Medical University, 
      Taipei 110, Taiwan.
FAU - Chen, Xiao-Yue
AU  - Chen XY
AD  - School of Respiratory Therapy, College of Medicine, Taipei Medical University, 
      Taipei 110, Taiwan.
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, Taipei 110, Taiwan.
FAU - Lee, Kang-Yun
AU  - Lee KY
AD  - Division of Pulmonary Medicine, Department of Internal Medicine, School of 
      Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
AD  - Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho 
      Hospital, Taipei Medical University, New Taipei City 235, Taiwan.
FAU - Chang, Jer-Hwa
AU  - Chang JH
AUID- ORCID: 0000-0002-1306-2089
AD  - School of Respiratory Therapy, College of Medicine, Taipei Medical University, 
      Taipei 110, Taiwan.
AD  - Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang 
      Hospital, Taipei Medical University, Taipei 110, Taiwan.
FAU - Chuang, Hsiao-Chi
AU  - Chuang HC
AUID- ORCID: 0000-0003-4651-5192
AD  - School of Respiratory Therapy, College of Medicine, Taipei Medical University, 
      Taipei 110, Taiwan.
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, Taipei 110, Taiwan.
AD  - Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho 
      Hospital, Taipei Medical University, New Taipei City 235, Taiwan.
AD  - Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei 
      Medical University, Taipei 110, Taiwan.
LA  - eng
GR  - DP2-110-21121-01-O-08/Ministry of Education/
GR  - 109-2314-B-038-093-MY3/Ministry of Science and Technology of Taiwan/
PT  - Journal Article
DEP - 20220810
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.21.36 (Pancreatic Elastase)
SB  - IM
MH  - Animals
MH  - *Emphysema/metabolism
MH  - Humans
MH  - *Mesenchymal Stem Cell Transplantation
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Mice
MH  - Pancreatic Elastase/metabolism
MH  - *Pulmonary Disease, Chronic Obstructive/pathology
MH  - *Pulmonary Emphysema/metabolism/therapy
MH  - Swine
MH  - Umbilical Cord
PMC - PMC9408173
OTO - NOTNLM
OT  - COPD
OT  - emphysema
OT  - hippo pathway
OT  - inflammation
OT  - lungs
COIS- The authors declare that they have no competing interest.
EDAT- 2022/08/27 06:00
MHDA- 2022/08/30 06:00
PMCR- 2022/08/10
CRDT- 2022/08/26 01:22
PHST- 2022/07/15 00:00 [received]
PHST- 2022/08/02 00:00 [revised]
PHST- 2022/08/06 00:00 [accepted]
PHST- 2022/08/26 01:22 [entrez]
PHST- 2022/08/27 06:00 [pubmed]
PHST- 2022/08/30 06:00 [medline]
PHST- 2022/08/10 00:00 [pmc-release]
AID - ijms23168906 [pii]
AID - ijms-23-08906 [pii]
AID - 10.3390/ijms23168906 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Aug 10;23(16):8906. doi: 10.3390/ijms23168906.