Evidence of Temporary Airway Epithelial Repopulation and Rare Clonal Formation by BM-derived Cells Following Naphthalene Injury in Mice

University of California, San Francisco, San Francisco, California, United States
The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology (Impact Factor: 1.54). 09/2007; 290(9):1033-45. DOI: 10.1002/ar.20574
Source: PubMed


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.

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Available from: Viacheslav Mikhailovich Mikhailov, Oct 14, 2014
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    • "In 2001, Krause and colleagues [26] published compelling evidence on the fact that a rare population of single BM-derived cells was able to repopulate the hematopoietic system and generate nonhematopoietic cell types in multiple tissues including epithelial cells of the liver, lung, skin, and gastrointestinal tract. Subsequently, several studies in murine models have demonstrated the ability of marrow-derived hematopoietic stem/progenitor cells (HSPCs) to home to the lung and engraft as airway and respiratory epithelial cells [30–33]. Others have shown that blood-borne stem cells may contribute to lung tissue in human recipients of bone marrow or lung transplantation [34–36]. "
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    ABSTRACT: Chronic lung diseases, such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD) are incurable and represent a very high social burden. Stem cell-based treatment may represent a hope for the cure of these diseases. In this paper, we revise the overall knowledge about the plasticity and engraftment of exogenous marrow-derived stem cells into the lung, as well as their usefulness in lung repair and therapy of chronic lung diseases. The lung is easily accessible and the pathophysiology of these diseases is characterized by injury, inflammation, and eventually by remodeling of the airways. Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal (stem) cells (MSCs), encompass a wide array of cell subsets with different capacities of engraftment and injured tissue regenerating potential. Proof-of-principle that marrow cells administered locally may engraft and give rise to specialized epithelial cells has been given, but the efficiency of this conversion is too limited to give a therapeutic effect. Besides the identification of plasticity mechanisms, the characterization/isolation of the stem cell subpopulations represents a major challenge to improving the efficacy of transplantation protocols used in regenerative medicine for lung diseases.
    Full-text · Article · Jan 2014 · The Scientific World Journal
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    • "The number of publications in The Anatomical Record that are related to regenerative medicine exploded in the 21st century. One paper, which reported temporary airway epithelial repopulation and rare clonal formation by mesenchymal stem cells after injury to the lung of mice (Serikov et al., 2007), provided the cover illustration for the Journal (Volume 290, 2007). Nearly 20 papers reported results for the cardiovascular system, including the heart (Eisenberg and Eisenberg, 2004; Rosen et al., 2004; Perez-Pomares et al., 2006). "

    Full-text · Article · Jan 2014 · The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology
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    • "In vivo experiments have shown the participation of BMSC in liver regeneration after CCl 4 injections [28]. There are also some data on the involvement of BMSC in lung airway epithelium renewal after chemical or bacterial damage [29] [30]. Nowadays the experiments on BMSC contribution to lung regeneration are being subjected to critical analysis [31]. "
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    ABSTRACT: The aim of this study was to clarify the regeneration mechanisms of thyroid in post-irradiated C57Bl/6 mice chimeric with transgenic green fluorescent protein (GFP) positive C57Bl/6 mice after 5 and 7.5Gy X-ray exposures with the aid of morphological and immunocytochemical research of GFP-positive cell distribution. Cryostat slides of larynxes with thyroid glands were fixed by mixture of cold methanol and ethanol, cell nuclei were stained with propidium iodide. After immunocytochemical staining the slides of larynx with thyroid gland were investigated by means of confocal LSM 5 PASCAL microscope. True GFP nature of green signals in tissue slides was confirmed via additional treatment by anti-GFP antibody and Texas Red labeled second antibody. Separate GFP-positive cells were observed in the walls of follicles and between follicles of chimeric mice 9-10 months after X-ray exposure. GFP signal was viewed as cytoplasmic droplets and within the colloid of follicles. The share of GFP-positive follicles reached 6.1±1.8%. There was also co-localization of GFP signals and positive staining for thyroglobulin by monoclonal antibody. As many as 20.8±1.8% among all propidium iodide positive blood cells and 52.3±8.3% among propidium iodide positive bone marrow cells were at the same time GFP-positive. In conclusion, the results show that the bone marrow stem cells participate in the thyroid gland regeneration after 5Gy X-ray exposure.
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