University of Vermont

Research at The University of Vermont

Setting a New Bar in Lung Regeneration Research

DANIEL WEISS, M.D., PH.D., PROFESSOR OF MEDICINE

In end-stage lung disease, transplantation is sometimes the only viable therapeutic option, but organ availability is limited and rejection presents an additional challenge. Innovative research efforts in the field of tissue regeneration, including pioneering discoveries by Daniel Weiss, M.D., Ph.D., and colleagues hold promise for this population, which includes an estimated 12.7 million people with chronic obstructive pulmonary disorder (COPD), the third leading cause of death in the U.S.

Lung tissue bioengineering, which involves the use of a scaffold — or framework — of lungs from human cadavers to engineer new lungs for patients with end-stage disease, is the current focus of Weiss and his team's work. In the past two years, he and colleagues have published a number of articles on the topic of stem cell-related lung regeneration, including six articles in Biomaterials, the leading bioengineering journal.

These studies have examined multiple perspectives on the process of stripping the cellular material from these lungs – called decellularizing — and replacing it with stem cells (recellularization), in an effort to grow new, healthy lungs for transplantation.

Working in animal and human models, Weiss and colleagues have addressed numerous challenges faced during the lung tissue bioengineering process, such as the storage and sterilization of decellularized cadaveric scaffolds and the impact of the age and disease state of donor lungs on these processes. In one of their most recent Biomaterials studies, the researchers reported on novel techniques that increase the ability to perform high-throughput studies of human lungs which allow researchers an opportunity to closely examine cell types, growth factors, and environmental influences like mechanical stretch — normal breathing motions — that affect successful lung recellularization.

Darcy Wagner, Ph.D., a postdoctoral fellow in Weiss' lab, developed a technique to dissect out and recellularize multiple, small segments in a biological/physiological manner that would take into consideration the appropriate three-dimensional interaction of blood vessels with the lung's airways and air sacs. Working with UVM biomaterials engineer Rachel Oldinski, Ph.D., the researchers further developed a new method using a nontoxic, natural polymer derived from seaweed to use as a coating for each lung segment prior to recellularization. This process allowed the team to selectively inject new stem cells into the small decellularized lung segments while preserving vascular and airway channels. Use of this technique, which resulted in a higher retention of human stem cells in both animal and human scaffolds, allows the small lung segments to be ventilated for use in the study of stretch effects on stem cell differentiation.

Through another novel technique — thermography or thermal imaging — Weiss and colleagues developed a noninvasive and non-destructive means for monitoring the lung scaffolds' integrity and physiologic attributes in real-time during the decellularization process. The method could be used as a first step in evaluating whether the lungs and eventual scaffolds are suitable for recellularization and transplantation.

This study and Weiss' related publications over the past year and a half showcase the positive impact of the $4.26 million National Institutes of Health Director's Opportunity for Research grant he received in October 2010. In addition to these scientific accomplishments, Weiss has forged strong industry ties, and has several patents pending.

Last modified May 19 2014 04:00 PM