Next Generation of Lung Stem Cell Research Takes Flight

September 8, 2017 by Jennifer Nachbur

Native stem cells in avian lungs.

Back in the early to mid-2000s, the term “stem cell” triggered excitement, but also controversy. However, the embryonic cells at the center of that debate were not the focus of work in the Division of Pulmonary and Critical Care Medicine at the University of Vermont (UVM), where researchers were examining the potential of using bone marrow-derived adult stem cells to repair damaged lung tissue in patients with several different lung diseases, including chronic obstructive pulmonary disease (COPD). 

For Daniel Weiss, M.D., Ph.D., UVM professor of medicine, that early work grew out of previous gene therapy research in cystic fibrosis (CF), a genetic disease that predominantly affects the lungs. He and UVM colleagues, including Benjamin Suratt, M.D., first had to prove that the adult stem cells could become lung cells in petri dishes. Then, they tested whether or not those stem cells would actually travel to the lung when introduced into the body. While several studies confirmed that those stem cells – which are capable of becoming many different kinds of cells in the body – did indeed go to the lung and initiate some repair, this didn’t happen often enough to have any potential clinical benefit. Nonetheless, these initial studies opened the door to a broad range of subsequent investigations which have offered new scientific insights and that have offered new potential clinical stem cell-based therapies. UVM’s work in the field attracted the attention and trust of not only lung-related foundations like the Cystic Fibrosis Foundation, but also of the National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI), which helped support the first international “Stem Cells and Lung Biology” conference at UVM in 2005 and the subsequent biennial symposiums that have taken place since then. The event had several goals, including the sharing of research findings among stem cell scientists from all over the world, the promotion of the development of clinical trials of cell therapies for pulmonary diseases and critical illnesses, and providing a forum for promising young researchers in the lung stem cell/bioengineering field.

Now 12 years later, UVM remains a leader in the area of “ex vivo” lung regeneration – lungs regenerated outside the body – and in cell-based therapies for lung diseases. Weiss’s work has garnered a number of significant grants, including a 2010 NIH Opportunity (ARRA stimulus) Grant that moved the work forward and supported the work of young scientists, as well as further funding from the NIH, Department of Defense, respiratory disease foundations, and industry.   Weiss, former postdoctoral fellow Darcy Wagner, Ph.D., (now an assistant professor at Lund University in Sweden) and colleagues in UVM’s Colleges of Medicine and Engineering and Mathematical Sciences, along with a number of collaborators at other institutions, have published a number of seminal studies on their techniques for decellularizing and recellularizing lung scaffolds, which addressed numerous challenges faced during the lung tissue bioengineering process (read more here).  Weiss and colleagues have also developed and published seminal work in developing other stem cell-based therapies for lung diseases.

“UVM also remains a leader in cell therapy approaches for lung diseases with significant progress in potential use in asthma, CF, and other lung diseases,” says Weiss. 

In addition, Professor of Medicine Jeffrey Spees, Ph.D., and former graduate students in his lab, including Krithika Rao, Ph.D.’15, have made significant strides in developing potential therapies for repairing the heart and vessels following heart attack (read more) and the work earned him a patent and recognition at the Invention2Venture conference in 2016.

Senior investigators like Weiss and his colleagues across the globe are working to ensure that the next generation of investigators is fully prepared to take this work well into the next quarter-century. The 7th Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases conference on July 24-27, 2017, which was chaired by Wagner, offered an expanded hands-on preconference workshop that provided opportunities for investigators and trainees to learn up-to-date techniques relevant for lung stem cell, cell therapy, and bioengineering work. A “Women and Diversity” reception at the symposium featured a panel and brought together attendees – roughly 50/50 representation from men and women at the conference for the first time ever – to create an action plan to change the culture for women and diversity in science. The 2017 conference had the highest number of women participants in the history of the conference.  

Several of Weiss’ female trainees, including postdoctoral associates Franziska Uhl, Ph.D., and Soraia Abreu, Ph.D., are active in lung stem cell and bioengineering research and also participated in the 2017 conference via poster presentations and instructing during the hands-on-session.

The conference also included an elevator pitch competition for trainees and junior investigators, including UVM’s Uhl and Sean Wrenn, M.D., a surgery resident who presented on the work he’s doing with Weiss to develop a novel lung-assist device based on bird lungs. Wrenn was the first-place winner of the competition, which had close to a dozen participants and was judged by a panel including: Yvonne Janssen-Heininger, Ph.D.; UVM professor of pathology; Kerry Swift, M.S., technology licensing officer in the UVM Office of Technology Commercialization; Erik Monsen, Ph.D., associate professor and Grossman Endowed Chair in Entrepreneurship in the UVM Grossman School of Business; Ghenima Dirami, Ph.D., of the NIH; Michael Matthay, M.D., of UCSF; and Finn Hawkins, MBBCH, of Boston University.

“The avian lung project is predicated upon taking design cues from nature and using it within the realm of biology and engineering to help address the severe problem of lung disease,” explains Wrenn, who adds that bird lungs have been found to have numerous structural and physiological advantages over mammalian (including human) lungs, which allow birds to fly at high altitudes with low oxygen content. “These wings may be helpful to mimic for oxygenation devices or even as transplantable artificially-engineered organs,” says Wrenn.

The Weiss lab has embarked upon pioneering studies using the avian lung studies to better understand these organs, using the same principles and techniques they have used to study and augment mammalian lungs. By learning what makes bird lungs different, but also what makes them similar, they can be used to help future people breathe better.

According to Weiss, the potential is limitless using these varied regenerative medicine techniques for lung diseases. One future goal for Weiss and colleagues is to develop a cross-campus program in regenerative medicine at UVM.