Detection of bone marrow–derived lung epithelial cells

Studies on the ability of bone marrow−derived cells to adopt the morphology and protein expression pattern of epithelial cells in vivo have expanded rapidly during the last decade, and hundreds of publications report that bone marrow−derived cells can become epithelial cells of multiple organs, including lung, liver, gastrointestinal tract, skin, pancreas, and others. In this review, we critically evaluate the literature related to engraftment of bone marrow–derived cells as epithelial cells in the lung. More than 40 articles focused on whether bone marrow cells can differentiate into lung epithelial cells have been published, nearly all of which claim to identify marrow-derived epithelial cells. A few investigations have concluded that no such cells are present and that the phenomenon of marrow-derived epithelial cells is based on detection artifacts. Here we discuss the problems that exist in published articles identifying marrow-derived epithelial cells, and propose standards for detection methods that provide the most definitive data. Identification of bone marrow−derived epithelial cells requires reliable and sensitive techniques for their detection, which must include cell identification based on the presence of an epithelial marker and the absence of blood cell markers as well as a marker for donor bone marrow origin. In order for these studies to be rigorous, they must also use approaches to rule out cell overlap by microscopy or single-cell isolation. Once these stringent criteria for identification of marrow-derived epithelial cells are used universally, then the field can move forward to address the critical questions about which bone marrow−derived cells are responsible for engraftment as epithelial cells, the mechanisms by which this occurs, whether these cells play a role in normal tissue repair, and whether specific cell subsets can be used for therapeutic benefit.