PMID- 34461993
OWN - NLM
STAT- MEDLINE
DCOM- 20211029
LR  - 20220830
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Aug 30
TI  - Intratracheal transplantation of trophoblast stem cells attenuates acute lung 
      injury in mice.
PG  - 487
LID - 10.1186/s13287-021-02550-z [doi]
LID - 487
AB  - BACKGROUND: Acute lung injury (ALI) is a common lung disorder that affects 
      millions of people every year. The infiltration of inflammatory cells into the 
      lungs and death of the alveolar epithelial cells are key factors to trigger a 
      pathological cascade. Trophoblast stem cells (TSCs) are immune privileged, and 
      demonstrate the capability of self-renewal and multipotency with differentiation 
      into three germ layers. We hypothesized that intratracheal transplantation of 
      TSCs may alleviate ALI. METHODS: ALI was induced by intratracheal delivery of 
      bleomycin (BLM) in mice. After exposure to BLM, pre-labeled TSCs or fibroblasts 
      (FBs) were intratracheally administered into the lungs. Analyses of the lungs 
      were performed for inflammatory infiltrates, cell apoptosis, and engraftment of 
      TSCs. Pro-inflammatory cytokines/chemokines of lung tissue and in bronchoalveolar 
      lavage fluid (BALF) were also assessed. RESULTS: The lungs displayed a reduction 
      in cellularity, with decreased CD45(+) cells, and less thickening of the alveolar 
      walls in ALI mice that received TSCs compared with ALI mice receiving PBS or FBs. 
      TSCs decreased infiltration of neutrophils and macrophages, and the expression of 
      interleukin (IL) 6, monocyte chemoattractant protein-1 (MCP-1) and 
      keratinocyte-derived chemokine (KC) in the injured lungs. The levels of 
      inflammatory cytokines in BALF, particularly IL-6, were decreased in ALI mice 
      receiving TSCs, compared to ALI mice that received PBS or FBs. TSCs also 
      significantly reduced BLM-induced apoptosis of alveolar epithelial cells in vitro 
      and in vivo. Transplanted TSCs integrated into the alveolar walls and expressed 
      aquaporin 5 and prosurfactant protein C, markers for alveolar epithelial type I 
      and II cells, respectively. CONCLUSION: Intratracheal transplantation of TSCs 
      into the lungs of mice after acute exposure to BLM reduced pulmonary inflammation 
      and cell death. Furthermore, TSCs engrafted into the alveolar walls to form 
      alveolar epithelial type I and II cells. These data support the use of TSCs for 
      the treatment of ALI.
CI  - (c) 2021. The Author(s).
FAU - Han, Junwen
AU  - Han J
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China.
FAU - Li, Gu
AU  - Li G
AD  - Department of Surgery, Brigham and Women's Hospital, Boston, MA, 02115, USA.
FAU - Hou, Minmin
AU  - Hou M
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
FAU - Ng, Julie
AU  - Ng J
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
FAU - Kwon, Min-Young
AU  - Kwon MY
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
FAU - Xiong, Kevin
AU  - Xiong K
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
FAU - Liang, Xiaoliang
AU  - Liang X
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
AD  - Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, 
      Baylor College of Medicine, Houston, TX, 77024, USA.
FAU - Taglauer, Elizabeth
AU  - Taglauer E
AD  - Department of Pediatrics, Division of Newborn Medicine, Boston Children's 
      Hospital, Boston, MA, 02115, USA.
FAU - Shi, Yuanyuan
AU  - Shi Y
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China.
FAU - Mitsialis, S Alex
AU  - Mitsialis SA
AD  - Department of Pediatrics, Division of Newborn Medicine, Boston Children's 
      Hospital, Boston, MA, 02115, USA.
FAU - Kourembanas, Stella
AU  - Kourembanas S
AD  - Department of Pediatrics, Division of Newborn Medicine, Boston Children's 
      Hospital, Boston, MA, 02115, USA.
FAU - El-Chemaly, Souheil
AU  - El-Chemaly S
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
FAU - Lederer, James A
AU  - Lederer JA
AD  - Department of Surgery, Brigham and Women's Hospital, Boston, MA, 02115, USA.
FAU - Rosas, Ivan O
AU  - Rosas IO
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
AD  - Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, 
      Baylor College of Medicine, Houston, TX, 77024, USA.
FAU - Perrella, Mark A
AU  - Perrella MA
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
AD  - Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, 
      MA, 02115, USA.
FAU - Liu, Xiaoli
AU  - Liu X
AUID- ORCID: 0000-0003-2904-4413
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham 
      and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. 
      xlliu@rics.bwh.harvard.edu.
AD  - Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, 
      MA, 02115, USA. xlliu@rics.bwh.harvard.edu.
LA  - eng
GR  - R01 HL130275/HL/NHLBI NIH HHS/United States
GR  - U01 AI138318/AI/NIAID NIH HHS/United States
GR  - U01AI38318/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210830
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - *Acute Lung Injury/chemically induced/therapy
MH  - Alveolar Epithelial Cells
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid
MH  - Lipopolysaccharides
MH  - Lung
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Stem Cells
MH  - *Trophoblasts
PMC - PMC8404310
OTO - NOTNLM
OT  - Acute lung injury
OT  - Alveolar epithelial cells
OT  - Engraftment
OT  - Inflammation
OT  - Trophoblast stem cells
COIS- The authors declare that they have no competing interests.
EDAT- 2021/09/01 06:00
MHDA- 2021/10/30 06:00
PMCR- 2021/08/30
CRDT- 2021/08/31 05:43
PHST- 2021/04/07 00:00 [received]
PHST- 2021/08/08 00:00 [accepted]
PHST- 2021/08/31 05:43 [entrez]
PHST- 2021/09/01 06:00 [pubmed]
PHST- 2021/10/30 06:00 [medline]
PHST- 2021/08/30 00:00 [pmc-release]
AID - 10.1186/s13287-021-02550-z [pii]
AID - 2550 [pii]
AID - 10.1186/s13287-021-02550-z [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2021 Aug 30;12(1):487. doi: 10.1186/s13287-021-02550-z.