The “Scientific Breakthroughs of the Year” session at ATS 2010 will not only highlight novel advances in the fields of stem cell research and regenerative medicine, but will also identify the ethical issues these advances are raising.

Currently, there are two clinical trials underway in North America involving stem cell therapy and pulmonary medicine—a Canadian trial for pulmonary hypertension and a U.S. trial for moderate to severe emphysema. According to Daniel Weiss, M.D., Ph.D., co-chair of the session and one of the investigators involved in the emphysema trial, other pulmonary and critical care targets for stem cell therapy being tested in mouse models include severe asthma, cystic fibrosis, acute respiratory distress syndrome (ARDS) and bronchiolitis obliterans.

“The Scientific Breakthroughs symposium is the International Conference’s premier scientific session, highlighting an area in pulmonary medicine research undergoing rapid progress with outstanding potential for clinical application,” said Thomas J. Mariani, Ph.D., who will co-chair the session with Blanca Camoretti-Mercado, Ph.D., and Dr. Weiss.

This session will feature internationally recognized scientist Darwin J. Prockop, M.D., Ph.D., professor of medicine and director of the Institute for Regenerative Medicine at Texas A&M University. Dr. Prockop is one of the pioneers of cell therapy and, in particular, has been instrumental in advancing cell therapy approaches for lung diseases. He has also served as an influential mentor for many in the field.

Dr. Prockop’s presentation, “Changing Paradigms for Therapy with Adult Stem/Progenitor Cells,” will examine the shift in thinking about how stem cells might be utilized in promoting health and preventing disease. He will also focus on solving problems that limit the effective therapeutic use of stems cells and surveying the advances and areas of interest in stems cells and regenerative medicine worldwide in order to give session attendees a better sense of the potential of these emerging therapies.

Following the presentation of related abstracts, Arthur Caplan, Ph.D., director of the Center for Bioethics at the University of Pennsylvania, will address the ethical issues that may be raised by stem cell therapies. He will also provide a framework for how healthcare professionals might work to resolve these ethical dilemmas.

Much of the controversy surrounding stem cells has focused on the use of embryonic stem cells, but there are other issues that are likely to be subjects for debate if stem cell therapy proves effective, including who are appropriate donors and whether stem cells themselves should be genetically modified to produce certain therapeutic outcomes. There is also the concern that stem cells, implicated in recent research on cancer, could turn into tumors in some patients many years after being introduced.

“It’s the absolute uncertainty of not knowing whether anything bad could happen as a result of the therapy,” said Dr. Weiss, “that poses some of the biggest ethical concerns.”  This in part, he added, is why only a few clinical trials involving the lungs have been conducted worldwide using stem cells. Researchers are taking a more cautionary approach than was taken generally a decade earlier with gene therapy.

“With no doubt,” said Dr. Camoretti-Mercado, “the promise of regenerative medicine has stimulated research on stem cells as a potential resource for cell-based therapy.”

“There has been an escalating interest in lung stem cells at the International Conference for the past five to seven years, particularly due to their potential to correct molecular abnormalities and/or promote tissue repair,” Dr. Mariani explained. “We currently find ourselves at a pivotal time, where we have access—either by production or purification—to multiple stem cell populations and substantial data in pre-clinical models suggesting that exogenous stem cells can ameliorate disease-related endpoints. It is at this time that we must seriously consider the biological and methodological issues of their clinical application, as well as the ethical implications of their study and use.”

The International Conference has received a growing number of abstracts on regenerative medicine, and more than 100 were submitted to the 2010 International Conference.

After the keynote presentations, four abstracts considered among the best submitted will be presented. Researchers will describe:

• the successful establishment of “clinical grade” cystic fibrosis-induced pluripotent stem (iPS) cells derived from dermal cells of a patient with CF;
• the restoration of fluid clearance function in endotoxin-injured human lungs through specific homing of intravenous injection of mesenchymal stem cells;
• the blockade of immune mediated mucus metaplasia in transplanted tracheas using a system that permits manipulation of embryonic trachea stem cells; and
• the reversal of hypoxia-induced pulmonary arterial hypertension and remodeling by limiting the contribution of bone marrow-derived progenitor cells to the lung using a kinase inhibitor.

“We are taking the first steps toward slowing or even blocking disease by interventions using stem cells,” Dr. Camoretti-Mercado said. “Although progenitor cells can be obtained, expanded and engineered ex vivo and reintroduced without immunomodulation into the recipient relatively easily, a challenge we face is the complexity of the lung and airway system. The respiratory system is comprised of more than 40 types of cells, unique structures and functions. Technically, it is difficult to analyze the lung at the genetic, biochemical, molecular and cellular levels. “However, clinical trials demonstrated potential benefit of autologous stem cell administration in patients with pulmonary hypertension; and a trial was initiated to study the effect of mesenchymal stem cells in patients with COPD.”

Planning this year’s session was a collaborative effort among a number of the Society’s assemblies. The symposium was developed jointly by the Assemblies on Respiratory Cell and Molecular Biology, Respiratory Structure and Function, and Allergy Immunology and Inflammation.

Experts to Concentrate on the Link Between Genetics and Respiratory Disease 

Two other sessions—Monday’s B6 “Genes that Cause Respiratory Disease,” and Tuesday’s C1 “Year in Review: Genetics of Lung Disease”—will also highlight the latest advances in these fields.

“I think one of the our most important goals during the 2010 International Conference is to provide attendees with a better appreciation of the study of genetics and how it may impact our specialty in the near future,” said Marc Moss, M.D., chair of the ATS International Conference Committee. “The best way to accomplish this is to highlight the outstanding research that pulmonary, critical care and sleep investigators are performing in this area.”

“Genes that Cause Respiratory Disease,” which will take place tomorrow from 8:15 to 10:45 a.m., will review the latest advances for pulmonary and critical care clinicians treating patients with inherited diseases of the alveolus, airways, pulmonary vasculature, chest wall and ventilatory control systems. “Many childhood-onset diseases with major respiratory morbidity, ranging from spinal muscular atrophy to primary ciliary dyskinesia, are now appreciated to be associated with specific gene defects,” said Paul E. Moore, M.D., director of pediatric allergy, immunology and pulmonary medicine at the Vanderbilt University School of Medicine, who will co-chair the session with Margaret W. Leigh, M.D., director of the University of North Carolina-Chapel Hill Cystic Fibrosis Center. “Yet, except in the case of cystic fibrosis, pulmonary providers often do not have an in-depth understanding of important new genetic information about the conditions they treat.” The symposium will provide attendees with cutting-edge information on recognizing and diagnosing inherited interstitial and alveolar lung disorders. It will also cover the implications of novel genetic findings in determining the pathobiology and novel potential treatments for childhood diseases like ciliary dyskinesia, asthma, pulmonary arterial hypertension, chest wall weakness and thoracic insufficiency, hypoventilation and disordered control of breathing.

Tuesday’s Year in Review session will feature a presentation on “Genetics of Lung Disease.” The session, which will take place from 8:15 to 10:15 a.m., will cover cutting-edge advances in the clinical and translational aspects of pulmonary rehabilitation, the respiratory health effects of smoking and the genetics of lung diseases like COPD, said session co-chair Kevin R. Flaherty, M.D., associate professor in the department of internal medicine at the University of Michigan Medical School.

“Each presenter will give a talk, followed by a five-minute segment for questions and answers,” he said. “The committee has selected speakers who are the best in their fields at what they do, so it should be a very interesting and informative session.”

Andrew L. Ries, M.D., who is professor of medicine and associate dean for academic affairs, and director of the pulmonary rehabilitation program at the University of California, San Diego, will discuss which patients benefit from pulmonary rehabilitation and how to clinically manage them.

Jonathan Samet, M.D., M.S., director of the Institute for Global Tobacco Control and co-director of the Risk Sciences and Public Policy Institute at Johns Hopkins University, and the chair of the Clean Air Scientific Advisory Committee for the U.S. Environmental Protection Agency, will talk about the respiratory health effects of smoking.

Edwin K. Silverman, M.D., Ph.D., associate professor of medicine at Harvard Medical School, will explain how smoking and genetic factors increase the risk of chronic lung disease, and will touch on the implications for clinical management and prevention.

Prescott Woodruff, M.D., M.P.H., assistant professor in residence at the University of California, San Francisco, will detail the best way to improve the diagnosis and management of COPD.