NHLBI Workshop
Cell Therapy for Lung Diseases

November 13-14, 2012


Executive Summary

Purpose

Acute and chronic lung diseases are leading causes of morbidity, mortality, and health care expenditures. Innovative approaches for therapies are urgently needed. Increasingly, patients who suffer from chronic lung diseases are seeking stem cell therapies outside the U.S. due to limited opportunities to participate in clinical studies of stem cells in the U.S. The current NHLBI portfolio on lung stem and progenitor cells has focused primarily on basic research to build fundamental knowledge of the role of stem/progenitor cells in lung disease and injury/repair. However, clinical application of cell therapy for lung diseases will require a more focused approach that coordinates basic research with translational research to facilitate cell-based clinical trials.

Therefore, the NHLBI convened a Cell Therapy for Lung Diseases working group on November 13-14, 2012 to make recommendations for future research directions. The workshop brought together investigators who study basic mechanisms including cell therapy in preclinical models of lung injury/disease along with clinical trial experts in cell therapy for cardiovascular indications and experts from NHLBI’s Production Assistance for Cell Therapy (PACT) program.

The overall objective was to discuss the current status of basic investigations in lung cell therapy, identify the scientific gaps in current knowledge regarding cell therapy in the treatment of lung diseases, and develop recommendations to the NHLBI and the research community on scientific priorities that would facilitate high quality, rigorous first-in-human trials of lung cell therapy.

Recommendations

The following high priority areas were recommended:

  1. What are the mechanisms by which mesenchymal stem (stromal) cells (MSCs) and other progenitor cells exert biological activity in vivo in both the mature and the immature lung?
  2. What are the cellular targets of administered MSCs and other cell-based preparations?
  3. Better characterization and methods of isolation of lung epithelial stem/progenitor cells in both the mouse and human lung are needed in order to assess the influence of MSCs and other cell therapy preparations on lung stem/progenitor cell function and the potential for treating lung diseases.
  4. What are the optimal modes of delivery of MSCs in terms of efficacy and safety? Do these differ for specific lung diseases?
  5. What are the goals of MSC and other cell based therapies on the prevention or treatment of specific adult and pediatric lung diseases?
  6. What is the potential for scalability of MSC and other cell based therapeutic preparations for sufficient expansion for large clinical trials?
  7. What are the mechanisms by which other stem and progenitor cell populations might have efficacy in lung repair and regeneration in both mouse and human lungs?
  8. What are the critical components of cell therapy products that impact safety and efficacy?
  9. There is a need to develop specific and sensitive assays to further define what cell characteristics are related to cell potency and develop minimum criteria that should be reported in clinical trials.

Opportunities:

  • The NHLBI supported Production Assistance for Cell Therapy (PACT) programs are a valuable resource for addressing many of the questions above. http://www.pactgroup.net/image of external icon
  • Organ procurement organizations (OPOs) in the US discard ~70-80% of lungs, which are deemed not viable for transplant. This wasted resource of human lungs could be ideal for the cell therapy research community to use for pre-clinical cell therapy studies.
  • Food and Drug Administration Pre-Investigational New Drug (IND) discussions are valuable and should be encouraged.
  • Utilize resources from clinical and translational science institutes (CTSI) to understand regulatory requirements for cell therapy.
  • Take advantage of FDA orphan market opportunities.
  • SMARRT program for FDA IND consultation prep. https://www.nhlbismartt.org/image of external icon

The group recommended that parallel paths of basic and clinical research should be taken to advance clinical testing of cell therapies in acute and chronic lung diseases in pediatric and adult diseases to facilitate bench to bedside and bedside to bench discoveries.

Chair

Michael Matthay, MD, University of California, San Francisco

Participants

Piero Anversa, M.D., Harvard Medical School
Jahar Bhattacharya, M.D., Ph.D., Columbia University Medical Center
Bruce K. Burnett, Ph.D., RAC, Duke University School of Medicine
Elizabeth Calle, MPhil, Yale University
Harold A. Chapman, M.D., University of California, San Francisco
Marilyn K. Glassberg MD, U. Miami Miller School of Medicine
Joshua M. Hare, M.D., U. Miami Miller School of Medicine
Derek J. Hei, Ph.D., University of Wisconsin - Madison
Andrew M. Hoffman, DVM., Tufts University
Jan Kajstura, PhD, Harvard Medical School
Stella Kourembanas, M.D., Harvard Medical School
David H. McKenna, M.D., University of Minnesota
Julio J. Mendez PhD, Yale School of Medicine
Marcelo M. Morales, MD, PhD, Federal University of Rio de Janeiro
Luis A. Ortiz, M.D., University Pittsburgh
Harald Ott, M.D., Massachusetts General Hospital
William Tente, M.S., Humacyte, Inc.
Bernard Thébaud, M.D., Ph.D., Research University of Ottawa
Bruce C. Trapnell,M.D., University of Cincinnati College of Medicine
Thomas Waddell, MD, MSc, PhD, University of Toronto
Daniel J. Weiss, M.D., Ph.D. University of Vermont College of Medicine
Jason X. -J. Yuan, M.D., Ph.D., University of Illinois at Chicago

Food and Drug Administration

Pakwai Au, Ph.D., Center for Biologics Evaluation and Research
Deborah A. Hursh, Ph.D., Center for Biologics Evaluation and Research
Allen K. Wensky, Ph.D., Center for Biologics Evaluation and Research
Keith Wonnacott, Ph.D. Center for Biologics Evaluation and Research

NHLBI Staff

  • Carol J. Blaisdell, M.D., Division of Lung Diseases
  • James Kiley, Ph.D., Division of Lung Diseases
  • Dorothy Gail, Ph.D., Division of Lung Diseases
  • Qing “Sara” Lin, Ph.D., Division of Lung Diseases
  • Liz Welniak, Division of Blood Disorders
  • Martha Lundberg, Division of Cardiovascular Sciences




Last Updated: January 2013




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