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

Abstract

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.

Airway and Alveoli Organoids as Valuable Research Tools in COVID-19

“…A final possibility when working with MS stem cells for lung organoids is to use mesenchymal stem cells as the starting point. Wang and collaborators 89 developed an alveolar organoid with epithelial stem/progenitor cells from mesenchymal cells obtained and isolated from the postnatal human lung, obtained from pediatric patients undergoing elective surgery for some airway abnormalities. This method may be used to study congenital lung lesions and alterations, and although this publication used pediatric-derived tissue, the use of adult isolated cells might replicate adult in vivo tissue.…”

Construction of transplantable artificial vascular tissue based on adipose tissue-derived mesenchymal stromal cells by a cell coating and cryopreservation technique

“…It was reported that the adventitial pericyte progenitor with MSC-like phenotype expressed CD90 with pericyte markers [48]. In addition, human lung tissue contained the pericyte-like subtype of MSCs with CD90 and pericyte marker expression [49]. Thus, it was considered that the same perivascular behavior of hASC subpopulations would be reproduced in our present study.…”

Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection

“…While this might look like a limitation, we believe it reflects best the situation in humans compared to inbred models. Secondly, we used the isolated LR-MSCs as a single population but previous single-cell transcriptomic studies demonstrated that MSC, are a rather heterogeneous population composed of distinct MSC subsets [8,9,72]. Third, due to the lung size, we analyzed three pooled specimens, representative of each lung region.…”

“…Primary pediatric MSCs were obtained as described previously [32,72]. Briefly, healthy lung tissue was obtained from pediatric patients undergoing elective surgery for congenital pulmonary airway malformation and other various airway abnormalities (n = 9, age range: 5 days to…”