title: Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury.
abstract: Chimerism on the parenchymal level has been shown for several human allografts, including liver, heart, and kidney, with the integrated recipient-derived cells most likely originating from multipotent bone marrow precursors. We investigated whether chimerism also occurs within epithelial structures of the lung. For this purpose archival tissue biopsies from seven explanted human lung allografts were obtained. We performed laser microdissection of the target structures with subsequent short tandem repeat analysis to detect chimerism within the isolated cells. We found integration of recipient-derived cells in the bronchial epithelium, in type II pneumocytes and in seromucous glands lying adjacent to larger bronchi in all lung allografts studied. Quantitative analysis revealed that the epithelial structures displaying signs of chronic injury, such as squamous metaplasia, showed a markedly higher degree of chimerism (24% versus 9.5%). We therefore conclude that in human lungs, epithelial chimerism occurs at least within bronchi, type II pneumocytes, and seromucous peribronchial glands. Although a bone marrow origin of immigrating host-derived stem cells has been suggested by previous studies in rodents, analysis of lung biopsies from bone marrow-transplanted patients (n = 3) could not prove such delineation in this study. The observation of an enhanced integration of recipient cells into chronically damaged epithelial structures suggests that extrapulmonary precursor cells are able to contribute to pulmonary regeneration.
authors.affiliation: Institute of Pathology, Division of Thoracic and Cardiovascular Surgery, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kleeberger
authors.forename: Anne
authors.initials: A
authors.lastname: Versmold
authors.forename: Thomas
authors.initials: T
authors.lastname: Rothämel
authors.forename: Sabine
authors.initials: S
authors.lastname: Glöckner
authors.forename: Martin
authors.initials: M
authors.lastname: Bredt
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology; D001980:Bronchi / Q000473:pathology*; D002675:Child, Preschool; D041322:Chromosomes, Human, Y; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000473:pathology*; D020545:Respiratory Mucosa / Q000473:pathology*; D018183:Transplantation Chimera