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STEM CELL GENETICS AND GENOMICS

Alteration of Marrow Cell Gene Expression, Protein Production, and Engraftment into Lung by Lung-Derived Microvesicles: A Novel Mechanism for Phenotype Modulation

^aDivision of Hematology and Oncology, Rhode Island Hospital, Providence, Rhode Island, USA;
^bRoger Williams Medical Center, Centers of Biomedical Research Excellence (COBRE), Providence, Rhode Island, USA;
^cDepartment of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA

Key Words. Adult bone marrow stem cells • Bone marrow transplantation • In vitro differentiation • Irradiation • Microvesicles

Correspondence: Jason M. Aliotta, M.D., Division of Hematology and Oncology and Division of Pulmonary, Critical Care and Sleep Medicine, Rhode Island Hospital, 3rd Floor, George Building, 593 Eddy Street, Providence, Rhode Island 02903, USA. Telephone: 401-456-5235; Fax: 401-456-5759; e-mail: jason_aliotta{at}brown.edu

Received February 19, 2007; accepted for publication May 17, 2007.
First published online in STEM CELLS EXPRESS   June 7, 2007.



Numerous animal studies have demonstrated that adult marrow-derived cells can contribute to the cellular component of the lung. Lung injury is a major variable in this process; however, the mechanism remains unknown. We hypothesize that injured lung is capable of inducing epigenetic modifications of marrow cells, influencing them to assume phenotypic characteristics of lung cells. We report that under certain conditions, radiation-injured lung induced expression of pulmonary epithelial cell-specific genes and prosurfactant B protein in cocultured whole bone marrow cells separated by a cell-impermeable membrane. Lung-conditioned media had a similar effect on cocultured whole bone marrow cells and was found to contain pulmonary epithelial cell-specific RNA-filled microvesicles that entered whole bone marrow cells in culture. Also, whole bone marrow cells cocultured with lung had a greater propensity to produce type II pneumocytes after transplantation into irradiated mice. These findings demonstrate alterations of marrow cell phenotype by lung-derived microvesicles and suggest a novel mechanism for marrow cell-directed repair of injured tissue.

Disclosure of potential conflicts of interest is found at the end of this article.

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