Epithelial Stem Cell Consortium

Building on the momentum in the field of stem cell research^* and the goal of developing a one-time cure for cystic fibrosis, the Cystic Fibrosis Foundation has formed an Epithelial Stem Cell Consortium. The consortium brings together investigators who will work collaboratively and share unpublished, emerging data through regularly scheduled teleconferences and meetings to identify challenges in the field and develop research approaches to address these challenges.

Focus

Consortium members are charged with enhancing the research community's ability to identify stem cells and understand how they function in epithelial tissues as a means to developing therapeutic approaches that can cure CF. The primary focus of this consortium is on lung stem cells, but it will also include efforts to branch into other tissues, such as the gastrointestinal system and pancreas. 

Members are encouraged to develop and share reagents and methodologies with the broader CF research community and participate in joint collaborations to advance research into the following priority areas:

• Characterization of airway basal/stem cells as a means for in-vivo therapeutic correction in people with CF
• Characterization of stem cell niches and how their manipulation may lead to therapeutic stem cell engraftment
• Development of long-term culture protocols for the differentiation of tissue progenitors and induced pluripotent stem cells (iPSC) to reconstitute airway epithelium in vivo

Identification of Target Cells for In-Vivo Gene Repair and Replacement

Successful strategies to repair or replace the defective cystic fibrosis transmembrane conductance regulator (CFTR) gene will require the ability to identify and target endogenous stem and progenitor cell populations that have the regenerative capacity to effectively repopulate affected epithelial tissues. Targeting these cell populations will be essential for ensuring the long-lived or even permanent treatment of people with CF.

In addition to understanding the basic biology of these cells, a priority for this group is to develop reagents and tools for the research community, such as antibodies against surface lung stem cell markers, cell lines, and engineered animal models that can be used to identify target cell populations.

Development of Ex-Vivo Cell-Based Therapies

In addition to in-vivo correction, ex-vivo applications are also being evaluated for their therapeutic potential. Using this approach, stem or progenitor cells may be manipulated ex vivo to correct the defective CFTR gene and then administered to a patient where engraftment into the appropriate tissue will be essential. Engraftment is viewed as a key obstacle that requires epithelial cell migration to -- and survival in -- the appropriate location within the epithelial surface.

Studies to define and test engraftment efficiency, particularly functional engraftment, into the appropriate stem cell niche in animal models and human lungs are necessary. Additionally, studies on the in-vivo expansion of engrafted cells and their ability to differentiate into appropriate cell types to produce a normal and functional epithelium are essential. Common pathways of “lung damage” or “niche stimulation” injury models, decellularized model systems, and zip code biology will require careful consideration for use in a damaged and inflamed CF lung setting.

Consortium Membership

 * The Foundation only funds research using adult stem cells.