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Lung Cells Transplanted to Irradiated Recipients Generate Lymphohematopoietic Progeny

Department of Pulmonary and Critical Care Medicine Section, Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska

Address correspondence to: J. G. Sharp, Ph.D., University of Nebraska Medical Center, Department of Genetics, Cell Biology and Anatomy, 986395 Nebraska Medical Center, Omaha, NE 68198-6395. E-mail: jsharp{at}unmc.edu

Bone marrow (stem) cells can differentiate into cells in multiple tissues, including lung. Conversely, there are reports that cells of nonhematopoietic tissues (brain, muscle) can give rise to lymphohematopoietic cells. Here we show that the lung contains cells capable of giving rise to lymphohematopoietic cells when transplanted to irradiated recipients. Whole lung cell suspensions, lung side population (SP) cells, and CD45^+/- lung cells obtained from male transgenic enhanced green fluorescent protein–expressing mice were transplanted intravenously to total body irradiated female mice. Green fluorescent cells were recovered from the circulation and phenotyped for their expression of lymphohematopoietic markers (CD3, CD4, CD8, B220, Gr-1, and Mac-1). Lung SP cells were composed of heterogeneous populations and had less ability to give rise to lymphohematopoietic cells than did bone marrow SP cells. Furthermore, the ability of cells from the lung of aged mice to generate lymphohematopoietic progeny was equivalent to that of cells from young mice. Cells from lung with radioprotective and lymphohematopoietic reconstituting abilities were CD45⁺. CD45⁺ cells in the lung cells have lymphohematopoietic stem/progenitor cell characteristics, and this has implications for cell or gene therapy applications.

Abbreviations: Dulbecco's modified Eagle's medium, DMEM • enhanced green fluorescent protein, EGFP • fluorescence-activated cell sorter, FACS • fetal calf serum, FCS • green fluorescent protein, GFP • Gray, Gy • Iscove's modified Dulbecco's medium, IMDM • phosphate-buffered saline, PBS • side population, SP

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