title: Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts.
abstract: The origin and turnover of connective tissue cells in adult human organs, including the lung, are not well understood. Here, studies of cells derived from human lung allografts demonstrate the presence of a multipotent mesenchymal cell population, which is locally resident in the human adult lung and has extended life span in vivo. Examination of plastic-adherent cell populations in bronchoalveolar lavage samples obtained from 76 human lung transplant recipients revealed clonal proliferation of fibroblast-like cells in 62% (106 of 172) of samples. Immunophenotyping of these isolated cells demonstrated expression of vimentin and prolyl-4-hydroxylase, indicating a mesenchymal phenotype. Multiparametric flow cytometric analyses revealed expression of cell-surface proteins, CD73, CD90, and CD105, commonly found on mesenchymal stem cells (MSCs). Hematopoietic lineage markers CD14, CD34, and CD45 were absent. Multipotency of these cells was demonstrated by their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. Cytogenetic analysis of cells from 7 sex-mismatched lung transplant recipients harvested up to 11 years after transplant revealed that 97.2% +/- 2.1% expressed the sex genotype of the donor. The presence of MSCs of donor sex identity in lung allografts even years after transplantation provides what we believe to be the first evidence for connective tissue cell progenitors that reside locally within a postnatal, nonhematopoietic organ.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan 48109-0360, USA. vlama@umich.edu
authors.forename: Vibha N
authors.initials: VN
authors.lastname: Lama
authors.forename: Lisa
authors.initials: L
authors.lastname: Smith
authors.forename: Linda
authors.initials: L
authors.lastname: Badri
authors.forename: Andrew
authors.initials: A
authors.lastname: Flint
authors.forename: Adin-Cristian
authors.initials: AC
authors.lastname: Andrei
authors.forename: Susan
authors.initials: S
authors.lastname: Murray
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Liao
authors.forename: Galen B
authors.initials: GB
authors.lastname: Toews
authors.forename: Paul H
authors.initials: PH
authors.lastname: Krebsbach
authors.forename: Marc
authors.initials: M
authors.lastname: Peters-Golden
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinsky
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003239:Connective Tissue Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008171:Lung Diseases / Q000145:classification / Q000601:surgery; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D008875:Middle Aged; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD