Research on 3D scaffolds sets new bar in lung regeneration
27 March 2014
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 University of Vermont (UVM) Professor of Medicine Daniel Weiss and colleagues, hold promise for this population.
Some well-designed studies have found a measured prevalence of chronic obstructive pulmonary disorder (COPD) in Europe between 4% and 10% of adults (Halbert et al, 2003). An increase from almost 270,000 European deaths in 2005 to 338,000 deaths by 2030 is expected, according to the European COPD Coalition.
Weiss and his team’s work focuses on the development of new methods and techniques for engineering lungs for patients with COPD and pulmonary fibrosis. This is being done through 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. Their studies have examined multiple perspectives on the process of stripping the cellular material from these lungs — called decellularising — and replacing it with stem cells (recellularisation), in an effort to grow new, healthy lungs for transplantation.
Working in animal and human models, Wagner and colleagues have addressed numerous challenges faced during the lung tissue bioengineering process, such as the storage and sterilisation of decellularised cadaveric scaffolds and the impact of the age and disease state of donor lungs on these processes.
In the past year alone, Weiss and colleagues published four articles in Biomaterials, the leading bioengineering journal, as well as two March 2014 articles by first author Dr Darcy Wagner, a postdoctoral fellow working in Weiss’ laboratory. In one of the latest Biomaterials studies, the researchers report on novel techniques that increase the ability to perform high-throughput studies of human lungs.
“It’s expensive and difficult to repopulate an entire human lung at one time and, unlike in mouse models, this doesn’t readily allow the study of multiple conditions, such as cell types, growth factors, and environmental influences like mechanical stretch — normal breathing motions — that will all affect successful lung recellularisation,” explained Weiss.
To address this, Wagner developed a technique to dissect out and recellularise 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 biomaterials scientist Dr Rachel Oldinski, UVM assistant professor of engineering, they further developed a new method using a non-toxic, natural polymer derived from seaweed to use as a coating for each lung segment prior to recellularisation. This process allowed the team to selectively inject new stem cells into the small decellularised lung segments while preserving vascular and airway channels. Use of this technique, which resulted in a higher retention of human stem cells in both porcine and human scaffolds, allows the small lung segments to be ventilated for use in the study of stretch effects on stem-cell differentiation.
“The ability to perform numerous experiments and screen multiple conditions from a single decellularised human lung provides an avenue to accelerate progress towards the eventual goal of regenerating functional lung tissue for transplantation,” said Wagner.
Through another novel technique — thermography or thermal imaging — Wagner and colleagues developed a non-invasive and non-destructive means for monitoring the lung scaffolds’ integrity and physiologic attributes in real-time during the decellularisation process. According to Wagner, this method could be used as a first step in evaluating whether the lungs and eventual scaffolds are suitable for recellularisation and transplantation. The development of these new techniques are “a significant step forward” in the field of lung regeneration, according to Wagner and her co-authors.
“This work serves as a core for helping develop a robust bioengineering effort to parallel ongoing stem-cell activities in the Department of Medicine and for fostering increasing collaborative efforts between colleges of medicine and engineering,” concluded Weiss.
Darcy E. Wagner, Nicholas R. Bonenfant, Dino Sokocevic, Michael J. DeSarno, Zachary D. Borg, Charles S. Parsons, Elice M. Brooks, Joseph J. Platz, Zain I. Khalpey, David M. Hoganson, Bin Deng, Ying W. Lam, Rachael A. Oldinski, Takamaru Ashikaga, Daniel J. Weiss. ‘Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration.’ Biomaterials, 2014; 35 (9): 2664 DOI: 10.1016/j.biomaterials.2013.11.078