Impaired angiogenic supportive capacity and altered gene expression profile of CD146+ mesenchymal stromal cells isolated from hyperoxia-injured neonatal rat lungs

Collins, Jennifer J. P.; Lithopoulos, Marissa A; Santos, Claudia C. dos; Issa, Nicolas C.; Moebius, M; Ito, Caryn Y.; Zhong, Sen; Vadivel, Arul; Thébaud, Bernard

doi:10.1183/13993003.congress-2018.lsc-1093

Cited by 3 publications

(4 citation statements)

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“…First, although our FACS panel enables us to properly discriminate and isolate mesenchymal cell subsets, it is limiting due to an inability to follow the trajectory of CD90 + CD146 + subset during chronic lung injury. In rodents, exposure to high oxygen levels disrupts the dual immune regulating and vascular supportive function of neonatal-lung derived CD146 + mesenchymal stromal cells (11). Similar findings were recently reported for a population of CD146 positive mesenchyme cells purified from human fetal lung when exposed to high levels of oxygen (38).…”

Section: Cd90 + Cd146 + Mesenchymal Cells In Copd Fail To Support Microvessel Formationsupporting

confidence: 73%

“…Recently, proliferation of NG2 + pericytes leading to excessive coverage of pulmonary capillaries and conversion to smooth muscle-like cells contributes, in part, to vascular remodeling found in human pulmonary arterial hypertension (48). MSCs, which derive from pericytes (10), are present in the tracheal aspirates of premature infants (11) and BALs of lung transplant recipients contributing to fibrotic obliteration of the small airways (12)(13)(14).…”

Section: Cd90 + Cd146 + Mesenchymal Cells In Copd Fail To Support Microvessel Formationmentioning

confidence: 99%

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CD90⁺CD146⁺ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

Wang

Dorn

Zeinali

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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Our understanding of mesenchymal cell subsets and their function in human lung affected by aging and in certain disease settings remains poorly described. We use a combination of flow cytometry, prospective cell-sorting strategies, confocal imaging, and modeling of microvessel formation using advanced microfluidic chip technology to characterize mesenchymal cell subtypes in human postnatal and adult lung. Tissue was obtained from patients undergoing elective surgery for congenital pulmonary airway malformations (CPAM) and other airway abnormalities including chronic obstructive pulmonary disease (COPD). In microscopically normal postnatal human lung, there was a fivefold higher mesenchymal compared with epithelial (EpCAM+) fraction, which diminished with age. The mesenchymal fraction composed of CD90+ and CD90+CD73+ cells was enriched in CXCL12 and platelet-derived growth factor receptor-α (PDGFRα) and located in close proximity to EpCAM+ cells in the alveolar region. Surprisingly, alveolar organoids generated from EpCAM+ cells supported by CD90+ subset were immature and displayed dysplastic features. In congenital lung lesions, cystic air spaces and dysplastic alveolar regions were marked with an underlying thick interstitium composed of CD90+ and CD90+PDGFRα+ cells. In postnatal lung, a subset of CD90+ cells coexpresses the pericyte marker CD146 and supports self-assembly of perfusable microvessels. CD90+CD146+ cells from COPD patients fail to support microvessel formation due to fibrinolysis. Targeting the plasmin-plasminogen system during microvessel self-assembly prevented fibrin gel degradation, but microvessels were narrower and excessive contraction blocked perfusion. These data provide important new information regarding the immunophenotypic identity of key mesenchymal lineages and their change in a diverse setting of congenital lung lesions and COPD.

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Section: Cd90 + Cd146 + Mesenchymal Cells In Copd Fail To Support Microvessel Formationsupporting

confidence: 73%

Section: Cd90 + Cd146 + Mesenchymal Cells In Copd Fail To Support Microvessel Formationmentioning

confidence: 99%

CD90⁺CD146⁺ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

Wang

Dorn

Zeinali

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In a study by C ollins et al . [19], which was selected from the 2018 Lung Science Conference in Estoril, Portugal, CD146+ lung mesenchymal stromal cells (L-MSCs) isolated from hyperoxia-injured rat lungs displayed an impaired angiogenic supportive capacity and altered gene expression profile, suggesting an active role for L-MSCs in BPD pathogenesis [20]. H irani et al .…”

Section: Molecular and Cellular Determinants Of The Developing Lungmentioning

confidence: 99%

Key paediatric messages from the 2018 European Respiratory Society International Congress

et al. 2019

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“…MSCs can differentiate into a variety of cells under different induction conditions, such as osteoblasts, chondroblasts, adipocytes, fibroblasts, myoblasts, endothelial cells, cardiomyocytes and neural tissue cells, which are the most deeply studied and widely used adult stem cells at present. [13][14][15] Studies have shown that MSCs can repair lung injury caused by many factors, including endotoxin, bleomycin, colchicine and hypoxia induced lung injury. 16,17 Sammour et al .…”

Section: Introductionmentioning

confidence: 99%

Peptide KLF14-P1 secreted from mesenchymal stem cells protects against bronchopulmonary dysplasia both in vivo and in vitro

Jiang

Zhang

Zhu

et al. 2022

Preprint

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Background: Mesenchymal stem cells (MSCs) have been confirmed to harbor therapeutic potential in bronchopulmonary dysplasia (BPD). Nevertheless, the possible influence of peptides secreted from MSCs remains clarified. Herein, this study focused on investigating the potential role of peptide KLF14-P1 (271TKHARRHP278, Named after the precursor protein Krueppel-like factor 14, KLF14) secreted from MSCs in BPD both in vivo and in vitro. Methods: Firstly, the mouse BPD model was constructed, and administrated with KLF14-P1 (10, 50 and 100 μg/g). General basic characteristics were observed. Pathological change of lung tissues was determined by HE analysis. Besides, the number and proportion of cells in broncho alveolar lavage fluid (BALF) were analyzed. The inflammatory factor (IL-1β, IL-6, TNF-α and IL-10) expressions in BALF and lung tissues were analyzed through ELISA, QRT-PCR and western blot. Moreover, MLE-12 cells stimulated with H2O2 (1 mM) was adopted construct in vitro BPD model. CCK-8, qRT-PCR, western blot and ELISA were carried out to evaluate the effects of KLF14-P1 (10, 50 and 100 μM) on H2O2-treated MLE-12 cell proliferation and inflammatory responses. The role of KLF14-P1 in the oxidative stress was evaluated by analysis. Results: In vivo, KLF14-P1 improved BPD mice accompanied with decreasing inflammatory infiltration and reducing lung dry / wet weight ratio. Moreover, in vitro, CCK-8 revealed that KLF14-P1 improved the viability MLE-12 cells treated with H2O2. In addition, KLF14-P1 notably inhibited the apoptosis of H2O2-treated MLE-12 cells. Besides, KLF14-P1 obviously ameliorated inflammatory responses of H2O2-treated MLE-12 cells. Conclusion: KLF14-P1 exhibited potential therapeutic properties against BPD.

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Impaired angiogenic supportive capacity and altered gene expression profile of CD146+ mesenchymal stromal cells isolated from hyperoxia-injured neonatal rat lungs

Cited by 3 publications

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CD90⁺CD146⁺ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

CD90⁺CD146⁺ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

Key paediatric messages from the 2018 European Respiratory Society International Congress

Peptide KLF14-P1 secreted from mesenchymal stem cells protects against bronchopulmonary dysplasia both in vivo and in vitro

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Impaired angiogenic supportive capacity and altered gene expression profile of CD146+ mesenchymal stromal cells isolated from hyperoxia-injured neonatal rat lungs

Cited by 3 publications

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CD90+CD146+ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

CD90+CD146+ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

Key paediatric messages from the 2018 European Respiratory Society International Congress

Peptide KLF14-P1 secreted from mesenchymal stem cells protects against bronchopulmonary dysplasia both in vivo and in vitro

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CD90⁺CD146⁺ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

CD90⁺CD146⁺ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung