Lung cells from neonates show a mesenchymal stem cell phenotype

• Published in: American journal of respiratory and critical care medicine 2007-06, Vol.175 (11), p.1158-1164
• Main Authors: HENNRICK, Kenneth T, KEETON, Angela G, THANNICKAL, Victor J, HERSHENSON, Marc B, NANUA, Suparna, KIJEK, Theresa G, GOLDSMITH, Adam M, SAJJAN, Umadevi S, BENTLEY, J. Kelley, LAMA, Vibha N, MOORE, Bethany B, SCHUMACHER, Robert E
• Format: Article
• Language: English
• Subjects: 5'-Nucleotidase - metabolism; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies; Antigens, CD - metabolism; Biological and medical sciences; Biomarkers; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Body fat; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Cartilage; Cell Adhesion; Cell Adhesion Molecules, Neuronal - metabolism; Cell Differentiation; Cell Movement; Cells, Cultured; Chemokine CCL2 - metabolism; Disease Progression; Endoglin; Enzyme-Linked Immunosorbent Assay; Fetal Proteins - metabolism; Fibroblasts; Fibroblasts - pathology; Flow Cytometry; Humans; Immunoblotting; Immunohistochemistry; Infant, Newborn; Infant, Premature; Intensive care medicine; Lung - pathology; Lung diseases; Medical sciences; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Phenotype; Premature babies; Premature birth; Proteins; Receptors, Cell Surface - metabolism; Respiration, Artificial; Respiratory distress syndrome; Respiratory Distress Syndrome, Newborn - genetics; Respiratory Distress Syndrome, Newborn - pathology; Respiratory Distress Syndrome, Newborn - therapy; Retrospective Studies; Smooth muscle; Stem cells; Telangiectasia, Hereditary Hemorrhagic; Thy-1 Antigens - metabolism; Trachea - pathology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Ventilators
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200607-941OC

Mesenchymal stem cells have been isolated from adult bone marrow, peripheral blood, adipose tissue, trabecular bone, articular synovium, and bronchial submucosa. We hypothesized that the lungs of premature infants undergoing mechanical ventilation contain fibroblast-like cells with features of mesenchymal stem cells. 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. 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. 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.