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Published ahead of print on March 1, 2007, doi:10.1164/rccm.200607-941OC
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American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 1158-1164, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200607-941OC


Original Article

Lung Cells from Neonates Show a Mesenchymal Stem Cell Phenotype

Kenneth T. Hennrick1, Angela G. Keeton1, Suparna Nanua1, Theresa G. Kijek1, Adam M. Goldsmith1, Umadevi S. Sajjan1, J. Kelley Bentley1, Vibha N. Lama2, Bethany B. Moore2, Robert E. Schumacher1, Victor J. Thannickal2 and Marc B. Hershenson1,3

Departments of 1 Pediatrics and Communicable Diseases, 2 Internal Medicine, and 3 Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan

Correspondence and requests for reprints should be addressed to Marc B. Hershenson, M.D., Medical Science Research Building II, Room 3570B, 1150 West Medical Center Drive, Box 0688, Ann Arbor, MI 48109-0688. E-mail: mhershen{at}umich.edu

Rationale: Mesenchymal stem cells have been isolated from adult bone marrow, peripheral blood, adipose tissue, trabecular bone, articular synovium, and bronchial submucosa.

Objectives: We hypothesized that the lungs of premature infants undergoing mechanical ventilation contain fibroblast-like cells with features of mesenchymal stem cells.

Methods: Tracheal aspirate fluid from mechanically ventilated, premature (< 30 wk gestation) infants 7 days old or younger was obtained from routine suctioning and plated on plastic culture dishes.

Measurements and Main Results: A total of 11 of 20 patients studied demonstrated fibroblast-like cells, which were identified as early as 6 hours after plating. Cells were found to express the mesenchymal stem cell markers STRO-1, CD73, CD90, CD105, and CD166, as well as CCR2b, CD13, prolyl 4-hydroxylase, and {alpha}-smooth muscle actin. Cells were negative for the hematopoietic and endothelial cell markers CD11b, CD31, CD34, or CD45. Tracheal aspirate monocyte chemoattractant protein-1/CCL2 levels were ninefold higher in aspirates in which fibroblast-like cells were found, and cells demonstrated chemotaxis in response to monocyte chemoattractant protein. Placement of cells into appropriate media resulted in adipogenic, osteogenic, and myofibroblastic differentiation. Patients from whom mesenchymal stem cells were isolated tended to require more days of mechanical ventilation and supplemental oxygen.

Conclusions: Together, these data demonstrate that tracheal aspirate fluid from premature, mechanically ventilated infants contains fibroblasts with cell markers and differentiation potential typically found in mesenchymal stem cells.

Key Words: bronchopulmonary dysplasia • fibroblast • monocyte chemoattractant protein • prematurity


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Mesenchymal stem cells have been shown in animal studies to home to sites of lung injury and reduce lung inflammation. Mesenchymal stem cells have been isolated from the human bronchial submucosa.

What This Study Adds to the Field
Cells with a mesenchymal stem cell phenotype can be isolated from the lungs of infants with respiratory distress syndrome.

 



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