Bioengineering is making major inroads on the path from basic science discoveries to practical lung regeneration in patients. Cellular and tissue engineering are still far removed from routine clinical use, but a variety of experimental lung platforms show promise for in vitro lung pathophysiological modeling and regeneration as well as early in vivo work in patients.

“There have been several major advances in the past four or five years related to the identification of a number of different progenitor cell populations in the distal lung capable of contributing to regeneration,” says Zea Borok, MD, chief of pulmonary and critical care medicine and director of the Hastings Center for Pulmonary Research at the University of Southern California Keck School of Medicine. “The continuing challenge in the field is how do we actually bring these new basic science advances to patients? We have to harness the basic science to improve outcomes in real diseases in the real world.”

Zea Borok, MD

Dr. Borok will co-chair today’s symposium with Barry Stripp, PhD, director of pulmonary stem cell research and professor of medicine and biomedical sciences at Cedars-Sinai Medical Center in Los Angeles.

Researchers have developed two different strategies to harness progenitor cells.

The most obvious way forward is to transplant progenitor cells and promote their proliferation and activity.

Another option is to explore the pathways that regulate progenitor cells and promote their survival in vivo, then exploit those pathways to protect and promote their regenerative activity.

“I think the lay public would like to believe that the answer is simply going to be delivering stem cells to the lung, and I don’t know that that’s correct, at least in the short-term,” Dr. Borok says. “Transplantation may be possible, but it’s the moon shot. Along the way, we are already learning how to improve the function of cells that can serve a progenitor function by identifying pathways that promote, protect, and improve their therapeutic activity.”

Two presenters will look at different strategies that allow researchers to screen for pathways that might improve progenitor cell function.

Christina Barkauskas, MD, assistant professor of medicine and affiliate of the Regeneration Next Initiative at Duke University School of Medicine, will explore the current uses and future promise of lung organoids. Kambez H. Benam, PhD, assistant professor of pulmonary sciences and critical care medicine at the University of Colorado at Denver will look at the latest in microfluidic technology used to model human airway disease by engineering airway-on-a-chip and breathing-smoking-lung-on-a-chip. Both of these approaches allow for screening of molecules that can affect progenitor cell function and differentiation to other cell types.

Xi Ren, PhD, assistant professor of biomedical engineering at Carnegie Mellon University, will discuss the latest developments in engineering native biomaterials for pulmonary regeneration. His laboratory is developing biologically and chemically selective approaches to modulating the extracellular matrix to boost pulmonary injury/repair and potentially whole-organ bioengineering.

Emmanuel Martinod, MD, PhD, professor of medicine at Descartes University, Paris, will discuss the latest advances in transplanting bioengineered tracheas.

Reinoud Gosens, PhD, assistant professor of translational pharmacology at the Groningen Research Institute for Asthma and COPD at the University of Groningen, The Netherlands, will take a different approach. Rather than implanting engineered organs, his laboratory is exploring strategies to modulate the WNT pathway as a mechanism to regenerate damaged lung tissue, for example, in chronic obstructive pulmonary disease.

“This is cutting-edge science,” Dr. Borok says. “We are finally getting to the stage where we can talk about engineering materials on which lung cells can actually survive and thrive and modulating the pathways that can make it happen. We may finally be looking at the beginnings of clinical cell therapy in respiratory medicine.”