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First published online June 7, 2007
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Submitted on February 19, 2007
Accepted on May 17, 2007

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

Jason M. Aliotta 1*, Fermin M. Sanchez-Guijo 2, Gerri J. Dooner 1, Kevin W. Johnson 1, Mark S. Dooner 1, Kenneth A. Greer 2, Deborah Greer 2, Jeffrey Pimentel 2, Luiz M. Kolankiewicz 2, Napoleon Puente 2, Sam Faradyan 2, Paulette Ferland 3, Elaine L. Bearer 3, Michael A. Passero 2, Mehrdad Adedi 2, Gerald A. Colvin 1, Peter J. Quesenberry 1

1 Rhode Island Hospital, Division of Hematology and Oncology, Providence, RI 02903 USA
2 Roger Williams Medical Center, Centers of Biomedical Research Excellence (COBRE), Providence, RI 02908 USA
3 Department of Pathology/Laboratory Medicine, Brown University, Providence, RI 02912 USA

* To whom correspondence should be addressed. E-mail: jason_aliotta{at}brown.edu.


  Abstract

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, radiationinjured 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. Lungconditioned medium 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 celldirected repair of injured tissue.

Key Words. Adult Bone Marrow Stem Cells, Bone Marrow Transplantation, In Vitro Differentiation, Irradiation, Microvesicles




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