Cells Derived from the Circulation Contribute to the Repair of Lung Injury

• Published in: American journal of respiratory and critical care medicine 2004-12, Vol.170 (11), p.1158-1163
• Main Authors: Abe, Shinji, Boyer, Craig, Liu, Xiangde, Wen, Fu Qiang, Kobayashi, Tetsu, Fang, Qiuhong, Wang, Xingqi, Hashimoto, Mitsuyoshi, Sharp, J. Graham, Rennard, Stephen I
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Differentiation - physiology; Cell Movement - physiology; Communication; Cytokeratin; Enzymes - adverse effects; Epithelial Cells - physiology; Fibroblasts; Fibroblasts - physiology; Hematopoietic Stem Cells - physiology; Intensive care medicine; Laboratories; Lung - physiopathology; Lung Diseases - etiology; Lung Diseases - physiopathology; Lungs; Medical sciences; Mice; Monocytes - physiology; Pancreatic Elastase - adverse effects; Parabiosis; Phosphatase; Proteins; Radiation; Radiation Pneumonitis - etiology; Radiation Pneumonitis - physiopathology; Respiratory Mucosa - physiopathology; Stem cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplants & implants; Whole-Body Irradiation - adverse effects; Wound Healing - physiology
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200307-908OC

Bone marrow (stem/progenitor) cells have been shown to "differentiate" into cells in multiple tissues, including lung. A low number of hematopoietic stem/progenitor cells also circulate in peripheral blood. The physiologic roles of these cells are still uncertain. This study was designed to test, using parabiotic mice that were joined surgically, whether stem/progenitor cells in blood contributed to the regeneration of lung after injury. Parabiotic mice were generated surgically by joining green fluorescent protein transgenic mice and wild-type littermates. These mice developed a common circulation (approximately 50% green cells in blood) by 2 weeks after surgery. The wild-type mouse was either uninjured or lethally irradiated or received intratracheal elastase or the combination of radiation with intratracheal elastase injection. Radiation or the combination of radiation with elastase significantly increased the proportion of bright green cells in the lungs of the wild-type mice. Morphologically, interstitial monocytes/macrophages, subepithelial fibroblast-like interstitial cells, and additionally type I alveolar epithelial cells immunostained for green fluorescent protein in wild-type mice. Approximately 5 to 20% of lung fibroblasts primary cultured from injured wild-type mice were green fluorescent protein expressing cells, indicating their blood derivation. This study demonstrates that stem/progenitor cells in blood contribute to the repair of lung injury in irradiated mice.