Workshop on Adult Stem Cells, Lung Biology, and Lung Disease Executive Summary

July 25-27, 2005

The National Heart, Lung, and Blood Institute (NHLBI), together with the Cystic Fibrosis Foundation, and the University of Vermont convened a meeting of investigators on July 25-27, 2005, in Burlington, Vermont to identify the opportunities for scientific advancement, including basic and clinical research, for cell-based therapy for lung diseases. Progress was presented by experts in stem cell biology, lung cell biology, and pulmonary medicine. Ideas were exchanged and strategies by which to accelerate studies on cell-based therapy in the lung were discussed.

This meeting stimulated lively discussions and, hopefully, some effective collaborations between clinician scientists and cell biologists. The consensus was that research on cell-based therapies for lung diseases should proceed with both basic and clinical investigations conducted in parallel, and should also include training for mutual education of clinician and basic scientists.

After the participants reviewed the current status of cell-based therapy in the lung, several recommendations on priorities for future research directions were generated.

The general recommendations of the workshop are:

• Support high quality translational studies focused on working towards cell-based therapy for human lung diseases. Pre-clinical models will provide proof of concept, however these must be relevant to the corresponding human lung disease. Disease specific models, particularly large animal models, should be developed for lung diseases.
• Rigorous techniques to unambiguously identify outcome measures should be incorporated into this research. Advanced techniques such as high resolution CT scanning and histomorphometry should be utilized where applicable. Pre-clinical models require functional outcome measures where clinical rigor should be applied e.g. pulmonary physiology/mechanics, electrophysiology, and other techniques.
• Proceed with design and implementation of initial, exploratory and safety investigations in patients with lung disease, where appropriate.
• Develop advanced histologic imaging techniques e.g. confocal microscopy with deconvolution, electron microscopy, laser capture dissection, etc. to avoid being mislead by current photomicroscopy and immunohistochemical approaches.
• Encourage new research to elucidate molecular programs for development of lung cell phenotypes, including mechanisms of epithelial/endothelial/mesenchymal interactions in development, and in the maintenance of reparative niches.
• Explore additional sources of stem/reparative cells such as adipose tissue, cord blood, endogenous lung tissue, skin and teeth. Uncover mechanisms of recruitment of, and phenotypic conversion to "reparative" cells.
• Identify additional cell surface markers which characterize reparative lung cell populations for use in visualization and sorting techniques .
• Develop in vitro assays which predict in vivo engraftment to screen selected populations of stem cells.
• Actively foster inter-institutional, multi-disciplinary research collaborations and consortiums as well as clinical/basic partnerships. Include a program of education on lung diseases and stem cell biology.
• Disseminate information about and encourage use of existing core services and facilities. A partial list includes NHLBI Production Assistance for Cellular Therapies (PACT), NCRR stem cell facilities, GMP Vector Cores, small animal mechanics and CT scanner facilities at several pulmonary centers.

Workshop Organizers and co-chairs

• Darwin Prockop , M.D., Ph.D. Tulane University Health Sciences Center, Co- chair
• Daniel Weiss, M.D., Ph.D. University of Vermont College of Medicine , Co-chair
• Zea Borok, M.D. University of Southern California , Keck School of Medicine, Session chair
• Jay K. Kolls, M.D. Children's Hospital of Pittsburgh , Session chair

NHLBI Staff:

• Mary Anne Berberich, Ph.D., Division of Lung Diseases
• Dorothy Gail, Ph.D., Division of Lung Diseases
• John Thomas, Ph.D. Division of Blood Diseases and Resources

Cystic Fibrosis Foundation:

• Christopher Penland, Ph.D.
• Robert J. Beall, Ph.D.

Participants:

• John H.T. Bates, Ph.D., University of Vermont College of Medicine
• Kenneth L. Brigham, M.D., Emory University School of Medicine
• Steven L. Brody, M.D., Washington University
• Bruce Bunnell, Ph.D., Tulane University Health Science Center
• Wellington V. Cardoso, M.D., Ph.D., Boston University
• Frances Carr, Ph.D., University of Vermont
• Pamela B. Davis, M.D., Ph.D., Case Western Reserve University
• Barbara Driscoll, Ph.D., Saban Research Institute of Children's Hospital Los Angeles
• Marie E. Egan, M.D., Yale University School of Medicine
• John F. Engelhardt, Ph.D., University of Iowa
• Michael Epperly, Ph.D., University of Pittsburgh
• John Evans, Ph.D., University of Vermont
• Alan Fine, M.D., Boston University
• Donald W. Fink, Jr., Ph.D., Food and Drug Administration (FDA)
• Barbara Grant, M.D., University of Vermont College of Medicine
• Brigid L. Hogan, Ph.D., Duke University
• Charles Irvin, Ph.D., University of Vermont College of Medicine
• Carla F. Bender Kim, Ph.D., Massachussetts Institute of Technology
• Darrell N. Kotton, M.D., Boston University
• Diane Krause, M.D., Ph.D., Yale University School of Medicine
• Douglas William Losordo, M.D., Tufts University
• Carolyn Lutzko, Ph.D., Children Hospital Los Angeles
• William J. Martin II, M.D., University of Cincinnati
• Dr. Michael Mengel, Institut Fuer Pathologie, Germany
• Marc B. Moss, M.D., Emory University
• Brooke T. Mossman, Ph.D., University of Vermont College of Medicine
• Luis A. Ortiz, M.D., University of Pittsburgh
• Polly E. Parsons, M.D., University of Vermont College of Medicine
• Sem H. Phan, M.D., University of Michigan
• Donald Phinney, Ph.D., Tulane University
• Matthew E. Poynter, Ph.D., University of Vermont College of Medicine
• Peter J. Quesenberry, M.D., Roger Williams Hospital, Rhodes Island
• Scott H. Randell, Ph.D., University of North Carolina at Chapel Hill
• Stephen I. Rennard, M.D., University of Nebraska
• Susan D. Reynolds, Ph.D., University of Pittsburgh
• Richard M. Rose, M.D., University of California, San Diego
• Steve D. Shapiro, M.D., Brigham & Women's Hospital
• Jeffrey L. Spees, Ph.D., University of Vermont College of Medicine
• Ducan J. Stewart, M.D., University of Toronto
• Robert M. Strieter, M.D., University of California, Los Angeles
• Barry R. Stripp, Ph.D., University of Pittsburgh
• Benjamin T. Suratt, M.D., University of Vermont College of Medicine
• Jakub Tolar, M.D., Ph.D., University Minnesota Medical School
• Anna M. Van Heeckeren, D.V.M., M.S., Case Western Reserve University
• Guoshun Wang, D.V.M., Ph.D., Louisiana State University Health Sciences
• David Warburton, M.D., Saban Research Institute of Children's Hospital Los Angeles
• Jeffrey A. Whitsett, M.D., Children's Hospital Research Foundation, Cincinnati
• Mary C. Williams, Ph.D., Boston University
• Lawrence N. Yager, Ph.D., National Center for Research Resources, NIH, DHHS

September 2005