Targeted cell replacement with bone marrow cells for airway epithelial regeneration

Wong, Amy P; Dutly, Andre E; Sacher, Adrian; Lee, Haeyul; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf; Hu, Jim; Waddell, Thomas K (2007). Targeted cell replacement with bone marrow cells for airway epithelial regeneration. American journal of physiology - lung cellular and molecular physiology, 293(3), L740-52. Bethesda, Md.: American Physiological Society 10.1152/ajplung.00050.2007

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It has been suggested that some adult bone marrow cells (BMC) can localize to the lung and develop tissue-specific characteristics including those of pulmonary epithelial cells. Here, we show that the combination of mild airway injury (naphthalene-induced) as a conditioning regimen to direct the site of BMC localization and transtracheal delivery of short-term cultured BMC enhances airway localization and adoption of an epithelial-like phenotype. Confocal analysis of airway and alveolar-localized BMC (fluorescently labeled) with epithelial markers shows expression of the pulmonary epithelial proteins, Clara cell secretory protein, and surfactant protein C. To confirm epithelial gene expression by BMC, we generated transgenic mice expressing green fluorescent protein (GFP) driven by the epithelial-specific cytokeratin-18 promoter and injected BMC from these mice transtracheally into wild-type recipients after naphthalene-induced airway injury. BMC retention in the lung was observed for at least 120 days following cell delivery with increasing GFP transgene expression over time. Some BMC cultured in vitro over time also expressed GFP transgene, suggesting epithelial transdifferentiation of the BMC. The results indicate that targeted delivery of BMC can promote airway regeneration.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery

UniBE Contributor:

Dutly, André Emanuel

ISSN:

1040-0605

ISBN:

17616650

Publisher:

American Physiological Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:01

Last Modified:

04 May 2014 23:18

Publisher DOI:

10.1152/ajplung.00050.2007

PubMed ID:

17616650

Web of Science ID:

000249125100030

URI:

https://boris.unibe.ch/id/eprint/26396 (FactScience: 70120)

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