Marrow cells as progenitors of lung tissue
Introduction
The capacity of bone marrow-derived cells to serve as precursors to differentiated cellular derivatives of various organs has challenged long-held views regarding the origin of somatic stem cells and the fixed nature of stem cell potential. Indeed, recent studies indicate that postnatal stem cells can form tissue structures previously held to originate from only one of the different embryonic cell layers. These apparent examples of so-called “trans-differentiation” have been noted in murine marrow transplantation experiments and in patients who underwent sex-mismatched bone marrow transplantations for hematological diseases. Engraftment as fully differentiated epithelial cells of the skin, gut, liver, and lung has been observed [1], [2], [3]. Recently, the entire phenomenon of trans-differentiation has been called into question. This is based on studies in mice whereby marrow-derived hepatocytes were found to arise as a result of cellular fusion between donor marrow cells and recipient hepatocytes [4]. One key-contributing element in all of these studies is tissue injury, whether in the form of pretransplantation total body irradiation, or localized injury to a specific target organ.
The overall relevance of these observations to normal organ function and the pathogenesis of specific disease states remain uncertain. Regardless, these observations have suggested a therapeutic strategy in which marrow cells are employed as an alternative source of progenitor cells for the replacement of specific cell types damaged or lost during disease. The relative ease of obtaining and purifying marrow cells makes this an attractive option.
Section snippets
Marrow-to-lung engraftment
To date, this field has been predominantly focused on the brain, heart, liver, and blood. Interest in lung has lagged because of intrinsic biologic and technical impediments. Firstly, the inherent cellular complexity of the lung along with the extremely slow turnover of lung parenchymal cells makes it difficult to study lung stem cells. Secondly, there are numerous difficulties associated with the histological analysis of an air-filled complex structure. Despite these limitations, several
Acknowledgements
This paper is based on a presentation at a Focused Workshop on “Stem Cell Plasticity” held in Providence, RI, April 8–11, 2003, sponsored by The Leukemia and Lymphoma Society, Roger Williams Medical Center, and the University of Nevada, Reno.
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