Epithelial Cells Derived from Swine Bone Marrow Express Stem Cell Markers and Support Influenza Virus Replication In Vitro

The bone marrow contains heterogeneous population of cells that are involved in the regeneration and repair of diseased organs, including the lungs. In this study, we isolated and characterized progenitor epithelial cells from the bone marrow of 4- to 5-week old germ-free pigs. Microscopically, the cultured cells showed epithelial-like morphology. Phenotypically, these cells expressed the stem cell markers octamer-binding transcription factor (Oct4) and stage-specific embryonic antigen-1 (SSEA-1), the alveolar stem cell marker Clara cell secretory protein (Ccsp), and the epithelial cell markers pan-cytokeratin (Pan-K), cytokeratin-18 (K-18), and occludin. When cultured in epithelial cell growth medium, the progenitor epithelial cells expressed type I and type II pneumocyte markers. Next, we examined the susceptibility of these cells to influenza virus. Progenitor epithelial cells expressed sialic acid receptors utilized by avian and mammalian influenza viruses and were targets for influenza virus replication. Additionally, differentiated type II but not type I pneumocytes supported the replication of influenza virus. Our data indicate that we have identified a unique population of progenitor epithelial cells in the bone marrow that might have airway reconstitution potential and may be a useful model for cell-based therapies for infectious and non-infectious lung diseases

Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche

Clinical and basic studies of cell-based myocardial therapy have proceeded at a rapid pace. Cell therapy could lead to successful cardiac regeneration or repair by any of three general mechanisms: differentiation of the administered cells into all of the cellular constituents of the heart; release of factors capable of paracrine signaling from the administered cells; and fusion of the administered cells with the existing constituents of the heart. Here, we argue that a fourth general mechanism could be operative: stimulation of endogenous repair by injected cells, which and might cause the regeneration of stem cell niches. In a porcine model of myocardial infarction, allogeneic mesenchymal stem cells stimulated substantial improvement in the ejection fraction, reduction of infarct size, and the growth of a rim of new cardiac tissue in the region in which the mesenchymal stem cells were injected. These effects occurred in the absence of definitive cardiac myocyte differentiation. After myocardial infarction, porcine hearts exhibit evidence of cardiac myocytes that have entered the cell cycle, neovascularization, and reduced levels of apoptosis. These data, in addition to new insights regarding the presence of endogenous cardiac stem cells, strongly support the concept that the heart could contain stem cell niches. Effective cell therapy could lead to restoration of these niches through multifaceted cell-cell interactions