Alveolar type II (ATII) cells have numerous functions related to lung homeostatsis; these include (i) acting as progenitors for alveolar type I (ATI) cells, which is particularly important during re-epithelialization of the lung after injury; (ii) synthesis and secretion surfactant proteins, which reduces surface tension and helps prevent collapse of the structures within the lung; and (iii) modulation of the immune system through the secretion of complement proteins and cytokines. Due to their important functions ATII cells are of particular interest for the development of cell transplantation therapeutics for the treatment of severe lung diseases. However, current methods for producing ATII cells from human embryonic stem (ES) cells are inefficient and require the formation or culturing of an embryoid body (EB), which produces a mixed population of cell derivatives and significantly increases the risk of teratoma formation after transplantation in vivo.
The inventors have developed a cell culture and a selection procedure which results reliably in an essentially pure population of human ATII cells without the use or formation of an EB. When transplanted into an animal model of lung injury ATII cells generated using this technique have been shown to accelerate the healing and return of lung function, as evidenced by restoration of blood arterial oxygen saturation levels.
This technology can be used to develop therapeutics for the treatment of pulmonary diseases and disorders, including acute lung injury, surfactant protein deficiencies of the lung, and cystic fibrosis.
3 patent applications have been filed: 12/527,969, 13/008, 637 and PCT/US2008/054553
Technology Ids: 2007-0031 and 2010-0017