Regenerative CF Airway Epithelium by Embryonic Stem Cells

Funding Type: 
SEED Grant
Grant Number: 
RS1-00466
ICOC Funds Committed: 
$0
Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
A major area of research in regenerative medicine is the potential application of cell therapy for various disorders. Human embryonic stem (ES) cells are self-renewable and are able to differentiate into various cell types, tissues and organs if they are properly taken care. Thus, ES cells can be a great resource for therapeutic treatment of a variety of dysfunction cells, tissues, and organs. However, it these cells are not properly taken care, when they are implanted to any tissues and organs they can give rise to the tumor formation. This research application focuses on two areas, one is to see if these cells can be trained in cell culture to direct their differentiated potential to lung epithelial cell types, the other focus is to see if such a training can reduce the risk of forming unwarranted tumor in immune-deficient mice. This is based on the hypothesis that human ES cells can be trained in cell culture toward lung epithelial cell types and these newly derived cells have a full capacity as lung epithelial cells. We will then use these modified ES cells to test the feasibility in cell culture system as well as in a tracheal graft repopulation model to see if these cells mixed with isolated adult cystic fibrosis (CF) cells can correct the chloride ion transport property, which is not function properly in CF. To achieve these goals, we will develop well-defined culture medium and condition for these cells to grow and to differentiate. We intend to use NIH approved human ES cell lines, H1 and H9 for this study. There are three specific aims in this application. Aim 1 is to define the defined (optimized) medium for these human ES cells to grow and to differentiate into lung and airway epithelial cell types. Aim 2 is then to put these trained cells to transplanted tracheal graft to see if these cells form differentiated lung/airway epithelium and the potential of forming tumor in the immune-deficient mice. Aim 3 is then mixed these trained cells with isolated CF cells in culture as well as in repopulating tracheal graft to see if the mixing can correct the chloride channel defect associated with CF. Success from such a study, not only proof of principal but also provides the justification to continue this research area for future cell therapy for this disease.
Statement of Benefit to California: 
A major area of research in regenerative medicine is the potential application of cell therapy for various disorders. Human embryonic stem (ES) cells are self-renewable and are able to differentiate into various cell types, tissues and organs if they are properly taken care. Thus, ES cells can be a great resource for therapeutic treatment of a variety of dysfunction cells, tissues, and organs. However, it these cells are not properly taken care, when they are implanted to any tissues and organs they can give rise to the tumor formation. In this research application, we would like to establish a proof of the principal that ES cells are indeed trainable and can be a great resource for cell therapeutic application. We focus on the possibility to use these ES-derived cells to correct the diseased phenotypes of airway/lung cells related to cystic fibrosis (CF). CF is a dreadful, genetic disease. One out of 25 Caucasians carries the defected CF gene. For California, there is a substantial population carrying the defected gene. The disease through the vicious cycles of infection and pneumonia in lung/airway resulting in many hospital visits, treatments, and care until there is no more drug can inhibit the bacteria infection. Currently, there is no cure. Attempts to use gene therapy and pharmacological agent for the treatment have met with little success. Human ES cells have a great potential to be used as the source for cell therapy, as these cells can be properly trained in vitro, as we intend to do. We think the feasibility to use this approach for cell therapy is very high since it has been reported in science literature that only 6-10% of wild-type cells are needed for CF airways. The current study used in vitro cell culture and transplant tracheal graft approach to see if these ES cells derived from cell culture manipulation can be useful for the correction of the CF defect. Thus, if this project is done successfully, the results will form the basis for future therapeutic application. Many Californian as well as CF patients will be benefited from this study.

© 2013 California Institute for Regenerative Medicine