The present invention relates to the discovery that different stem cell types (e.g., bone marrow-derived mesenchymal stem cells (BM-MSC) and adipose-derived mesenchymal stem cells (AT-MSC)) undergo large changes in lung epithelial marker expression depending on the substrate on which they are cultured. The present invention includes methods and compositions for differentiating of mesenchymal stem cells, such as bone marrow and adipose tissue mesenchymal stem cells, into lung cells, populations of lung cells, and methods of alleviating or treating a lung defect in a subject in need thereof.