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

Wang, Limei; Dorn, Patrick; Zeinali, Soheila; Froment, Laurène; Berezowska, Sabina; Kocher, Gregor J; Alves, Marco P; Brügger, Melanie; Esteves, Blandina I.O.; Blank, Fabian; Wotzkow, Carlos; Steiner, Selina; Amacker, Mario; Peng, Ren-Wang; Marti, Thomas Michael; Guenat, Olivier T.; Bode, Peter Karl; Moehrlen, Ueli; Schmid, Ralph Alexander and Hall, Sean Ralph Robert (2020). CD90+CD146+ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung. American journal of physiology - lung cellular and molecular physiology, 318(4), L813-L830. American Physiological Society 10.1152/ajplung.00146.2019

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BACKGROUND Our understanding of mesenchymal cell subsets and their function in human lung affected by aging and in certain disease settings remain poorly described. METHODS We use a combination of polychromatic 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). RESULTS Using polychromatic flow cytometry, there was a 5-fold higher fraction of EpCAM-CD45-CD31-CD14- (mesenchymal) compared with EpCAM+CD45-CD31-CD14- cells (epithelial) in unaffected postnatal human lung. The mesenchymal fraction was composed primarily of single CD90+ and CD90+CD73+ cells both enriched in niche factors CXCL12 and PDGFRα. Immunofluorescence confirmed CD90+ cells in close proximity to EpCAM+ cells some co-staining for pro-SPC in the alveolar region suggestive of an alveolar unit. Contained within the CD90+ population, a subset co-expressed the pericyte marker CD146 with immunomodulatory properties able to internalize influenza virosomes, as well as live influenza virus. Postnatal CD90+CD146+ mesenchymal cells supported microvessel formation, whereas CD90+CD146+ mesenchymal cells from COPD patients failed to do so. In congenital lung lesions, cystic airspaces and dysplastic alveolar regions were marked with an expanded underlying thick interstitium of CD90+ and CD90+PDGFRα+ cells. CONCLUSION These data provide important new information regarding the immunophenotypic identity of key mesenchymal lineages and track their change in diverse setting of congenital lung lesions and other airway abnormalities including COPD.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Live Cell Imaging (LCI)
10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research > ARTORG Center - Organs-on Chip Technologies

UniBE Contributor:

Wang, Limei; Dorn, Patrick; Zeinali, Soheila; Berezowska, Sabina Anna; Kocher, Gregor; Oliveira Esteves, Blandina Isabel; Blank, Fabian; Wotzkow Alvarez, Carlos; Steiner, Selina Katja; Peng, Ren-Wang; Marti, Thomas and Schmid, Ralph

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology

ISSN:

1040-0605

Publisher:

American Physiological Society

Language:

English

Submitter:

Heidi Lobsiger

Date Deposited:

26 Feb 2020 11:05

Last Modified:

04 Apr 2020 01:33

Publisher DOI:

10.1152/ajplung.00146.2019

PubMed ID:

32073879

Uncontrolled Keywords:

CD90 COPD congenital lung malformations mesenchymal vasculogenesis

BORIS DOI:

10.7892/boris.140881

URI:

https://boris.unibe.ch/id/eprint/140881

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