Study on 3D scaffolds sets new bar in lung regeneration

March 8, 2014 by Jennifer Nachbur
Study on 3D scaffolds sets new bar in lung regeneration
Darcy Wagner, Ph.D., postdoctoral fellow in medicine/pulmonary, left and Daniel Weiss, M.D., Ph.D., professor of medicine. Credit: Raj Chawla, UVM Medical Photography

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, M.D., Ph.D., and colleagues, holds 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.

In the past year alone, Weiss and colleagues published four articles in Biomaterials, the leading journal, as well as two March 2014 articles by first author Darcy Wagner, Ph.D., a postdoctoral fellow working in Weiss' lab, reporting their development of new methods and techniques for engineering lungs for patients with COPD and pulmonary fibrosis.

Weiss and his team's work focuses on 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, 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 Biomaterials studies, "Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of 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 scientist Rachel Oldinski, Ph.D., UVM assistant professor of engineering, 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 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 for transplantation," says 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 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.

The development of these new techniques are "a significant step forward" in the field of lung regeneration, say Wagner and her coauthors.

This study and Weiss' and Wagner's related publications over the past 15 months showcase the positive impact of the $4.26 million National Institutes of Health (NIH) Director's Opportunity for Research grant Weiss received in October 2010 as part of the American Recovery and Reinvestment Act funding. In addition to these scientific accomplishments, he's forged strong industry ties, as well, and has several patents pending.

"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 the Colleges of Medicine and Engineering," says Weiss.

Explore further: Lungs clothed in fresh cells offer new hope for transplant patients

Related Stories

Lungs clothed in fresh cells offer new hope for transplant patients

February 1, 2012
For patients suffering from severe pulmonary diseases including emphysema, lung cancer or fibrosis, transplantation of healthy lung tissue may offer the best chance for survival. The surgical procedure, however, faces two ...

Research team successfully grows human lung in lab

February 18, 2014
(Medical Xpress)—A team of researchers with the University of Texas has, for the first time, successfully grown a human lung in a lab. Project leads Dr. Joaquin Cortiella and Dr. Joan Nichols announced the landmark breakthrough ...

US researchers identify first human lung stem cell

May 11, 2011
For the first time, researchers at Brigham and Women's Hospital (BWH) have identified a human lung stem cell that is self-renewing and capable of forming and integrating multiple biological structures of the lung including ...

Tracking nanodiamond-tagged stem cells

August 5, 2013
A method that is used to track the fate of a single stem cell within mouse lung tissue is reported in a study published online this week in Nature Nanotechnology. The method may offer insights into the factors that determine ...

New clues found to preventing lung transplant rejection

February 25, 2014
Organ transplant patients routinely receive drugs that stop their immune systems from attacking newly implanted hearts, livers, kidneys or lungs, which the body sees as foreign.

Recommended for you

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

New vaccine production could improve flu shot accuracy

July 24, 2017
A new way of producing the seasonal flu vaccine could speed up the process and provide better protection against infection.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.