e13504 Background: Marrow cells engrafted into irradiated mice form pulmonary epithelial type II pneumocytes. The capacity to do this is influenced by marrow cell cycle. Marrow derived pulmonary epithelial cells after transplantation are increased three fold at the G1/S interface. Methods: We have also shown that microvesicles derived from irradiated lung tissue enter marrow cells resulting in expression of mRNAs for surfactants A-D, clara cell-specific protein and aquaporin 5 and that cell entry is a prerequisite. Marrow cells interacted with lung-derived microvesicles also show an increased capacity for forming pulmonary epithelial cells after marrow transplantation. Results: We have also shown that marrow stem cells do not have a stable phenotype. They alter their phenotype continuously with cell cycle passage and that the most primitive marrow stem cells are an actively cycling population. Purified marrow stem cells, designated aslong-term hematopoietic stem cells (LT-HSC) are in fact mostly in G0, but when whole unseparated marrow is studied, using either Hoechst 33342/Pyronin Y separations or tritiated thymidine suicide followed by competitive engraftment into lethally irradiated mice, over 50% of these long-term engrafting cells are in S/G2/M. Given that these studies are at either an instantaneous point in time or over a 30 minute time interval, this indicates that the marrow stem cell population is a cycling population This explains the observations that marrow stem cell phenotype is continually changing with regard to marrow renewal, differentiation, marrow homing, and gene expression. Lung-derived microvesicles differentially enter marrow stem cells at different points in cell cycle adding another layer to the complexity of cell fate determination for marrow stem cells. Conclusions: Altogether, these observations indicate that microvesicle cell modulation probably explains the phenomena of stem cell plasticity. Furthermore, the marrow stem cell population is differentially modulated at different points in cell cycle by microvesicle exposure. These observations suggest a complex regulatory system for marrow stem cells with a stable population but continually changing individual components. This represents a new biology.