Fetal pulmonary cells and uses thereof
Isolated mixed populations of fetal pulmonary cells, engineered three-dimensional tissue constructs of these cells, and uses thereof in identifying therapeutic agents which augment, repair, and/or replace dysfunctional native lung and to perform in vitro studies such as pharmaceutical screening, models for lung development and disease and characterization of chemical or mechanical injury are provided.
1. An engineered three-dimensional pulmonary tissue construct comprising: 1) a mixed population of fetal pulmonary cells, wherein said population comprises epithelial, endothelial, and mesenchymal cells, wherein said cells exhibit enhanced viability and proliferation, 2) a three-dimensional matrix of natural polymer hydrogels comprising collagen or elastin, wherein said matrix is permissive to cell-cell and cell-growth factor interactions, and 3) a combination of fibroblast growth factors (FGF) comprising FGF10, FGF7, and FGF2, wherein the combination of FGF10/7/2 induces robust budding of epithelial structures and the formation of uniform endothelial networks in parallel.
2. The engineered three-dimensional pulmonary tissue construct of claim 1 , wherein the three-dimensional matrix comprises MATRIGEL™ or a mixture of a synthetic polymer and collagen or elastin.
3. The engineered three-dimensional pulmonary tissue construct of claim 1 further comprising mast cells.
4. A method for engineering pulmonary tissue with a functional, perfused vascular network comprising implanting into an animal the engineered three-dimensional pulmonary tissue construct of claim 1 .