Evidence of temporary airway epithelial repopulation and rare clonal formation by BM-derived cells following naphthalene injury in mice.
The goal of the study was to investigate participation of bone marrow (BM) cells in the process of airway epithelial restoration after naphthalene-induced injury. We transplanted sex-mismatched green fluorescent protein (GFP) -tagged BM-derived cultured plastic-adherent mesenchymal stem cells into 5Gy-irradiated C57BL/6 recipients. After 1 month of recovery, experimental animals were subjected to 250 mg/kg naphthalene IP. Animals were killed at 2-30 days after naphthalene. By immunofluorescence, immunohistochemistry, and by in situ hybridization for the Y-chromosome, we observed patches of donor-derived cells in the large and small conducting airways, mostly at 2-6 days after injury. GFP(+) cells in the epithelium of airways were positive for pancytokeratin and some other epithelial markers. Although rare, GFP(+) cells formed clear isolated patches of the bronchial epithelium, consistent with clonal formation; as some cells were also positive for proliferating cell nuclear antigen, a marker of proliferating cells. After day 12, only occasional GFP(+) cells were present in the epithelium. These data confirm that bone marrow-derived cultured mesenchymal cells can participate in the recovery of the injured airway epithelium after naphthalene-induced injury with minimal long-term engraftment.
Serikov
Vladimir B
VB
Children's Hospital Oakland Research Institute, Oakland, California 94609, USA. vserikov@chori.org
Popov
Boris
B
Mikhailov
Viacheslav M
VM
Gupta
Naveen
N
Matthay
Michael A
MA
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009281:Naphthalenes; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012038:Regeneration; D020545:Respiratory Mucosa / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014916:Whole-Body Irradiation
D009281:Naphthalenes; D018809:Proliferating Cell Nuclear Antigen; D049452:Green Fluorescent Proteins; C031721:naphthalene