Abstract: Culture systems and methods for long term culture of mammalian tissues are provided. Tissues include but are not limited to lung alveolar tissue, stomach tissue, pancreas tissue, bladder tissue, liver tissue, and kidney tissue. Cultures are initiated with fragments of mammalian tissue, which are then cultured embedded in a gel substrate that provides an air-liquid interface. Cultured explants of the invention can be continuously grown in culture for a year or more, while maintaining features of the tissue including prolonged tissue expansion with proliferation, multilineage differentiation, and recapitulation of cellular and tissue ultrastructure.