| Incomplete reprogramming after fusion of human multipotent stromal cells and bronchial epithelial cells. | |
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MedLine Citation:
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PMID: 20724526 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bone marrow-derived progenitor cells can fuse with cells of several different tissues, including lung, especially following injury. Despite many reports of cell fusion, few studies have examined the function of the resulting hybrid cells. We cocultured human multipotent stromal cells (hMSCs) and normal human bronchial epithelial cells (NHBEs) and observed the formation of hMSC/NHBE heterokaryons. The heterokaryons expressed several proteins characteristic of epithelial cells, such as keratin and occludin. Hybrid cells also expressed the mRNAs and proteins for 2 important ion channels that maintain bronchial and alveolar fluid balance: the cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial Na(+) channel (ENaC). By immunocytochemistry, CFTR was expressed in many hybrid cells but was absent or low in others. Whole-cell patch-clamp recordings demonstrated a glibenclamide-sensitive current in the presence of barium chloride, consistent with functional CFTR channels, in control NHBEs and hMSC/NHBE heterokaryons. Total cell capacitance measurements showed that the membrane surface area of heterokaryons was similar to that of NHBEs. Heterokaryons expressed the α- and γ-ENaC subunits but did not express the β-ENaC subunit, indicating the inability to form a complete ENaC channel. In addition, hybrid cells formed by the fusion of hMSCs with immortalized bronchial cells that expressed CFTR ΔF508 did not lead to reprogramming of the hMSC nucleus and expression of wild-type CFTR mRNA. Our data show that reprogramming can be incomplete following fusion of adult progenitor cells and somatic cells and may lead to altered cell function. |
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Authors:
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Ingrid M Curril; Masayo Koide; Calvin H Yang; Alan Segal; George C Wellman; Jeffrey L Spees |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-19 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 24 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-02 Completed Date: 2011-01-04 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 4856-64 Citation Subset: IM |
Affiliation:
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Cell and Molecular Biology Program and Vermont Lung Center, Burlington, Vermont, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Bronchi
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cytology Cell Fusion Cell Membrane / metabolism Cells, Cultured Cystic Fibrosis Transmembrane Conductance Regulator / metabolism Electrophysiology Epithelial Cells / cytology*, metabolism* Flow Cytometry Humans Immunohistochemistry Multipotent Stem Cells / cytology*, metabolism* Nuclear Reprogramming / genetics, physiology* Reverse Transcriptase Polymerase Chain Reaction Stromal Cells / cytology*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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P20 RR-155557/RR/NCRR NIH HHS; R01-HL-085210/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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