The present invention provides processes for producing a bioengineered lung (BEL) from an acellular lung matrix that has been treated with growth hormones, seeded with primary lung cells, and cultured in a bioreactor. Also provided are BELs and methods of transplanting the BEL into a subject in need of a lung transplant, and methods for using BELs for the study of the lung microbiome and its role in lung development and remodeling.

The present invention provides processes for producing a bioengineered lung (BEL) from an acellular lung matrix that has been treated with growth hormones, seeded with primary lung cells, and cultured in a bioreactor. Also provided are BELs and methods of transplanting the BEL into a subject in need of a lung transplant, and methods for using BELs for the study of the lung microbiome and its role in lung development and remodeling.

Described herein are methods and compositions for regulation of the p53 pathway, providing intrinsic “sternness” allowing for their efficient in vitro expansion following isolation. Pharmacologic approaches to modulate p53 signaling supports expansion of stem cells, including greater clonal expansion of lung stem cells when compared to use of other small molecules such as ROCK inhibitor Y27632 alone. Effects of combined treatment with Pifithrin-α and Y27632 are additive. The current invention involves use of drugs that target the p53 pathway to reversibly regulate stem cell expansion in vitro for banking of stem cells and for pre-conditioning of stem cells prior to orthotopic transplantation.

Described herein are methods and compositions for regulation of the p53 pathway, providing intrinsic “sternness” allowing for their efficient in vitro expansion following isolation. Pharmacologic approaches to modulate p53 signaling supports expansion of stem cells, including greater clonal expansion of lung stem cells when compared to use of other small molecules such as ROCK inhibitor Y27632 alone. Effects of combined treatment with Pifithrin-α and Y27632 are additive. The current invention involves use of drugs that target the p53 pathway to reversibly regulate stem cell expansion in vitro for banking of stem cells and for pre-conditioning of stem cells prior to orthotopic transplantation.

Using lung tissues as a source, mammalian lung progenitor cells lung spheroids and lung spheroid cells (LSCs) were prepared. In one embodiment mammalian LSCs were prepared by (i) culturing mammalian lung tissue explant cells under adherent culture conditions to form a first lung cell outgrowth culture; (ii) culturing the first lung cell outgrowth culture under low-adherence conditions to form lung spheroids; and (iii) culturing the lung spheroids under adherent culture conditions so as to form LSCs. The low-adherence conditions may be a cell culture or suspension. The lung spheroids or LSCs may be formulated into pharmaceutical compositions. Uses such as treatment of lung diseases or diagnostics are also provided. Lung spheroids and LSCs represents a simple and highly reproducible method to generate therapeutic lung cells.

Using lung tissues as a source, mammalian lung progenitor cells lung spheroids and lung spheroid cells (LSCs) were prepared. In one embodiment mammalian LSCs were prepared by (i) culturing mammalian lung tissue explant cells under adherent culture conditions to form a first lung cell outgrowth culture; (ii) culturing the first lung cell outgrowth culture under low-adherence conditions to form lung spheroids; and (iii) culturing the lung spheroids under adherent culture conditions so as to form LSCs. The low-adherence conditions may be a cell culture or suspension. The lung spheroids or LSCs may be formulated into pharmaceutical compositions. Uses such as treatment of lung diseases or diagnostics are also provided. Lung spheroids and LSCs represents a simple and highly reproducible method to generate therapeutic lung cells.

Provided herein are methods and compositions for identifying ionocytes from respiratory epithelial cells, and uses of such cells for treatment of inflammatory lung disease. Also provided herein are methods and compositions for modulating respiratory tract epithelial cell proliferation, differentiation, maintenance, and/or function.

Provided herein are methods and compositions for identifying ionocytes from respiratory epithelial cells, and uses of such cells for treatment of inflammatory lung disease. Also provided herein are methods and compositions for modulating respiratory tract epithelial cell proliferation, differentiation, maintenance, and/or function.

Compositions, materials, devices and methods are disclosed for the use of decellularized avian lung scaffolds for potential xenotransplantation and other uses including use as novel lung assist or bridge-to-transplant devices and as potential alternatives to current ECMO devices and technologies. Decellularization of an avian lung and recellularization with human lung cells is described.

Described herein are methods and compositions related to induced alveolar epithelial type 2 cells (iAEC2s), e.g., artificially-produced epithelial type 2 cells.