Derivation of multipotent airway basal cells (iBCs) from pluripotent stem cells

Basal cells in the airway are unique in that they have stem cell properties that can mature into many cell types needed for proper functioning of the airway. Given the self-renewal stem cell properties of airway basal cells, they are ideal candidate for regenerative medicine as they can generate airway cells to restore airway function. In addition to their biological function in the airway, basal cells are used for modeling of airway diseases and drug development as they can be expanded in vitro under proper growing condition. Well-established protocols are needed to generate these basal cells in vitro. The use of primary bronchial epithelial cells provides an unpredictable source of cells that is problematic for cell-based therapies and produces limited quantity of cells. Directed differentiation of induced pluripotent stem cells (iPSCs, or adults cells that are programmed to embryonic stem cell-state) into basal cells is complicated by lengthy and complex protocols resulting in cell types that do not process the stem cell properties.Through careful and thorough understanding of cell maturation in lung development, we developed methodologies to not only derive airway basal cells from iPSCs but also expand these cells in vitro and cryopreserve these cells. The process involves isolation of lung progenitor or parental cells and expansion of the isolated cells through the airway development program with key activating molecules followed by purification of the cells with a specific marker. The resulting basal cells process key stem cell properties in vitro to give rise to other cell types and can be applied for airway disease modeling studies. This efficient derivation of airway basal cells from iPSCs overcomes many hurdles of current iPSC technology to aid in the study of airway diseases.Boston University is seeking licensing partners to commercialize this technology Thomas J McMurry 617-358-4550

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