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 The consortium brings together investigators who will work collaboratively and share unpublished, emerging data through regularly scheduled teleconferences and meetings to identify challenges in the field and develop research approaches to address these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.
Consortium members are charged with enhancing the research community's ability to identify stem cells and understand how they function in the airway epithelium as a means to developing therapeutic approaches that can cure CF.
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
- Development of long-term culture protocols for the differentiation of tissue progenitors and induced pluripotent stem cells (iPSC) to reconstitute airway epithelium in vivo
- Development of engraftment models and strategies to facilitate transplantation of stem cells into the airway epithelium
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 models that will be used to test the function of long-lived multipotent stem/progenitor cells. The goal is to develop a "gold standard" model for the field that will be used for testing the efficacy of in vivo gene therapy and/or cell replacement strategies.
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/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.
|Brian Davis, PhD||University of Texas Health Science Center at Houston|
|John Engelhardt, PhD||University of Iowa|
|Adam Feinberg, PhD||Carnegie Mellon University|
|Brigitte Gomperts, MD||University of California, Los Angeles|
|Finn Hawkins, PhD||Boston University School of Medicine|
|Jed Mahoney, PhD||Cystic Fibrosis Foundation Therapeutics Lab|
|Scott Randell, PhD||University of North Carolina at Chapel Hill|
|Susan Reynolds, PhD||Nationwide Children's Hospital|
|Amy Ryan (Firth), PhD||University of Southern California|
|Jason Spence, PhD||University of Michigan|
|Barry Stripp, PhD||Cedars-Sinai Medical Center|
* The Foundation only funds research using adult stem cells.