CD45/CD11b positive subsets of adult lung anchorage-independent cells harness epithelial stem cells in culture

Yakov Peter, Namita Sen, Elena Levantini, Steven Keller, Edward P. Ingenito, Aaron Ciner, Robert Sackstein, Steven D. Shapiro

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between stem/progenitor cells that proliferate or differentiate and somatic cells of the lung, we used a novel organotypic ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free-floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3 and β7, and constituted 37% of the total culture at day 14, yielding a mixed yet conservative population that recapitulated RNA expression patterns of the healthy lung. AICs exhibited rapid proliferation manifested by a marked 60-fold increase in cell numbers by day 21. More than 50% of the AIC population was c-KIT+ or double-positive for CD45+ and CD11b+ antigenic determinants, consistent with cells of hematopoietic origin. The latter subset was found to be enriched with prosurfactant protein-C and SCGB1A1 expressing putative stem cells and with aquaporin-5 producing cells, characteristic of terminally differentiated alveolar epithelial type-1 pneumocytes. At the air/gel interface, AICs undergo remodeling to form a cellular lining, whereas TGF(β)1 treatment modifies protein expression properties to further imply a robust effect of the microenvironment on AIC phenotypic changes. These data confirm the active participation of clonogenic hematopoietic stem cells in a mammalian model of lung repair and validate mixed stem/somatic cell cultures, which license sustained cell viability, proliferation and differentiation, for use in studies of compensatory pulmonary growth.

Original languageEnglish (US)
Pages (from-to)572-583
Number of pages12
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 1 2013

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Keywords

  • Anchorage-independent cells
  • CD45/CD11b positive cells
  • Lung progenitors
  • Suspension culture

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

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