Lung Regeneration: Research on 3D Scaffolds Sets New Bar

03/10/2014
Photo: Lung

The researcher team works focuses on lung tissue bioengineering, which involves the use of a scaffold of lungs from human cadavers to engineer new lungs for patients with end-stage disease; © panthermedia.net/
Sebastian Kaulitzki

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) Prof. Daniel Weiss and colleagues, holds promise for this population.

Weiss and his team's work focuses on 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 decellularizing – and replacing it with stem cells (recellularization), in an effort to grow new, healthy lungs for transplantation.

Working in animal and human models, Dr. Darcy Wagner, 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 the latest studies, "Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration," 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 recellularization," explains Weiss.

To address this, Wagner 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 biomaterials scientist Dr. Rachel Oldinski, they 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 porcine (pig) 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 decellularized human lung provides an avenue to accelerate progress towards the eventual goal of regenerating functional lung tissue for transplantation," says Wagner, first author of the study.

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 decellularization process. According to Wagner, this method could be used as a first step in evaluating whether the lungs and eventual scaffolds are suitable for recellularization and transplantation.

MEDICA.de; Source: University of Vermont