Nav: Home

Columbia engineers and clinicians first to build a functional vascularized lung scaffold

August 30, 2017

New approach to bioengineering lungs selectively treats epithelium that lines the lung airway, while preserving lung vasculature; this transformative technique could lead to improved care of patients with lung disease

New York, NY--August 30, 2017--End-stage lung disease is the third leading cause of death worldwide, accounting for 400,000 deaths per year in the United States alone. Researchers exploring new ways to both promote lung repair and increase the number of available donor lungs have been challenged by the organ's extreme complexity--the lung has more than 40 different cell types residing in its matrix and the total surface area between the airway and the vasculature is the size of a tennis court. Efforts to bioengineer functional lungs from fully decellularized or synthetic scaffolds that lack functional vasculature have been largely unsuccessful until now.

A Columbia Engineering team led by Gordana Vunjak-Novakovic, University Professor and the Mikati Foundation Professor at Columbia Engineering and professor of medical sciences (in Medicine) at Columbia University, and N. Valerio Dorrello, assistant professor of pediatrics at Columbia University Medical Center, is the first to successfully bioengineer a functional lung with perfusable and healthy vasculature in an ex vivo rodent lung. Their new approach (DOI 10.1126/sciadv.1700521), which allows the removal of the pulmonary epithelium while maintaining the viability and function of the vascular network and the lung matrix, is published today in Science Advances.

In the past seven years, several research groups have been able to fully decellularize lungs to build scaffolds for lung bioengineering with the proper architecture and stiffness that can be repopulated by newly introduced cells. To rebuild a functional lung from this cell-free scaffold, researchers need to regenerate both the epithelial surfaces in the airway and the endothelial lining of the vasculature. An intact vascular network--missing in these scaffolds--is critical not only for maintaining the blood-gas barrier and allowing for proper graft function, but also for supporting the cells introduced to regenerate the lung. This has proved to be a daunting challenge.

"We developed a radically new approach to bioengineering of the lung," says Vunjak-Novakovic, a pioneer in tissue engineering who directs the Laboratory for Stem Cells and Tissue Engineering. "We reasoned that an ideal lung scaffold would need to have perfusable and healthy vasculature, and so we developed a method that maintains fully functional lung vasculature while we remove defective epithelial lining of the airways and replace it with healthy therapeutic cells. This ability to selectively treat the pulmonary epithelium is important, as most lung conditions are diseases of the epithelium."

Earlier techniques for decellularization of the entire lung were designed to remove all cells from the lung, generating a cell-free lung scaffold. The Columbia team has now demonstrated a transformative approach to obtaining functional vascularized lung grafts. They developed an airway-specific method to remove the pulmonary epithelium while preserving the lung vasculature, matrix and other supporting cell types such as fibroblasts, myocytes, chondrocytes, and pericytes. Following lung cannulation in a rodent lung, they ventilated the lungs and perfused them on an ex vivo lung perfusion system (EVLP), similar to the extracorporeal membrane oxygenation (ECMO) system utilized to support patients with cardiovascular and respiratory failure. They then delivered intratracheally a mild detergent solution to an isolated single lung to remove epithelial cells and protected the vasculature by circulating a perfusate containing electrolytes and energy substrates. The lung scaffold maintained the bronchial and vascular architecture, and supported the attachment and growth of human adult and stem cell-derived pulmonary cells in this ex vivo bioreactor.

"Every day, I see children in intensive care with severe lung disease who depend on mechanical ventilation support. The approach we established could lead to entirely new treatment modalities for these patients, designed to regenerate lungs by treating their injured epithelium" says Dorrello, the lead author of the study.

"Strategies aimed at increasing the number of transplantable lungs would have an immediate and profound impact," says Matthew Bacchetta, associate professor of surgery, Columbia University Medical Center, and a co-author of the paper. "Lung transplantation is the only definitive treatment we have for patients with end-stage lung disease, but there is a severe shortage of donor organs--only 20 percent of potential donor lungs are acceptable for transplantation and this leads to many potentially avoidable deaths on the waiting list. In addition, early intervention with gene or cell therapy may offer even greater benefits by promoting lung repair and regeneration, thus slowing the progression of disease and ultimately avoiding the need for transplantation. This approach could also serve as a means to make the donor lung more resilient and durable for transplantation. As a lung transplant surgeon, I am very excited about the great potential of our technique."

The study has been supported by a new $8.2M seven-year grant from the National Institutes of Health that focuses on modeling, pathogenesis, and treatment of idiopathic pulmonary fibrosis. The team is already using their controllable model of lung regeneration to treat human lungs ex vivo, and for further study of lung development and repair in the context of the whole organ. They are developing new modalities for imaging-guided cell removal and delivery of therapeutic cells or agents for clinical applications. They are also refining targeted, localized, and selective treatment of the defective pulmonary epithelium to address the clinical needs for specific lung diseases.

"This is a major step forward in bioengineering lungs," Vunjak-Novakovic says. "The creation of de-epithelialized whole lungs with functional vasculature may open new frontiers in lung bioengineering and regenerative medicine. This project could not have been successfully completed without the interdisciplinary effort that made us step out from our zone of comfort, and try novel approaches in collaboration with bioengineers, clinical scientists, and stem cell scientists."
About the Study

The study is titled, "Functional vascularized lung grafts for lung bioengineering." The contributors are N. Valerio Dorrello (Department of Pediatrics, Columbia University Medical Center CUMC, and Department of Biomedical Engineering, Columbia Engineering), Brandon A. Guenthart (Department of Biomedical Engineering, Columbia Engineering, and Department of Surgery, CUMC), John D. O'Neill (Department of Biomedical Engineering, Columbia Engineering), Jinho Kim (Department of Biomedical Engineering, Columbia Engineering), Katherine Cunningham (Department of Biomedical Engineering, Columbia Engineering), Ya-Wen Chen (Columbia Center for Human Development and Department of Medicine, CUMC), Mauer Biscotti (Department of Surgery, CUMC), Theresa Swayne (Herbert Irving Comprehensive Cancer Center, CUMC), Holly M. Wobma (Department of Biomedical Engineering, Columbia Engineering), Sarah X. L. Huang (Columbia Center for Human Development and Department of Medicine, CUMC), Hans-Willem Snoeck (Columbia Center for Human Development and Department of Medicine, Columbia Center for Translational Immunology, and Department of Microbiology and Immunology, CUMC), and Matthew Bacchetta (Department of Surgery, CUMC).

This work was supported by the National Institutes of Health (P41 EB002520 to G.V.-N and U01HL134760 to H-W.S and G.V.-N.), Driscoll Children's Fund and Hearts of ECMO (Extracorporeal Membrane Oxygenation) (to N.V.D.), the Mikati Foundation (to G.V.-N.), and the Richard Bartlett Foundation (to M.B.).

H.-W.S., S.X.L.H., and Y.-W.C. are authors on a patent application related to this work filed by Columbia University (application no. PCT/US2013/051913, filed 24 July 2013). M.B., B.G., J.D.O ad G.V-N. are authors on a patent application related to this work filed by Columbia University (application no.1425387, filed 4 April, 2014). J.K., J.D.O. and G.V.-N. are authors on a patent application related to this work filed by Columbia University (invention report CU 17293, filed 9. February 2016).The other authors declare that they have no other competing interests.


Paper: DOI 10.1126/sciadv.1700521

Columbia Engineering

Columbia Engineering is one of the top engineering schools in the U.S. and one of the oldest in the nation. Based in New York City, the School offers programs to both undergraduate and graduate students who undertake a course of study leading to the bachelor's, master's, or doctoral degree in engineering and applied science. Columbia Engineering's nine departments offer 16 majors and more than 30 minors in engineering and the liberal arts, including an interdisciplinary minor in entrepreneurship with Columbia Business School. With facilities specifically designed and equipped to meet the laboratory and research needs of faculty and students, Columbia Engineering is home to a broad array of basic and advanced research initiatives, from the Columbia Nano Initiative to the Columbia Genome Center. These interdisciplinary centers in science and engineering, big data, nanoscience, and genomic research are leading the way in their respective fields while our engineers and scientists collaborate across the University to solve theoretical and practical problems in many other significant areas.

Columbia University School of Engineering and Applied Science

Related Transplantation Articles:

Study provides clues to improving fecal microbiota transplantation
Results from a placebo-controlled trial provide a strategy for improving fecal microbiota transplantation (FMT) for patients with recurrent Clostridium difficile infection.
Brazil faces major challenges in liver transplantation
A recent analysis indicates that more than 1,700 liver transplantations are performed annually in Brazil.
These days fecal transplantation is no joke
Fecal transplants are increasingly being used to treat certain human illnesses and there has been a dramatic increase in animal experiments involving fecal material.
Transplantation and cell therapy
Key leaders in the field of cellular therapy will highlight new applications to potentially cure patients with blood diseases and infections on the occasion of the 5th Cell Therapy Day.
Elsevier announces the launch of Transplantation Reports
Elsevier, a world-leading provider of scientific, technical, and medical information products and services today announces the launch of Transplantation Reports, a new online-only open access journal covering all areas of transplantation.
Common cause for complications after kidney transplantation identified
The BK polyomavirus often causes complications after kidney transplantation. The research group of Professor Hans H.
Uterine transplantation: Subjects have 'adjusted well to their new life situation'
In October last year the Gothenburg, Sweden, group of Mats Brannstrom announced the world's first live birth following the transplantation of a donated uterus.
The road to successful uterus transplantation to restore fertility
Swedish clinicians recently reported the first live birth after uterus transplantation, which was followed by two more uneventful births and another pregnancy that is near term.
After lung transplantation: Go back to work and feel better
In an original article in Deutsches Ärzteblatt International, Hendrik Suhling and coauthors report the findings of the first study ever performed in Germany on the percentage of lung-transplant patients who resume employment after transplantation and the reasons that keep the others from going back to work.
Size of biomarker associated with improved survival following transplantation
Among patients with severe aplastic anemia who received stem cell transplant from an unrelated donor, longer leukocyte (white blood cells) telomere length (a structure at the end of a chromosome) was associated with increased overall survival at five years, according to a study in the Feb.

Related Transplantation Reading:

Handbook of Kidney Transplantation
by Dr. Gabriel M. Danovitch MD (Author)

Concise, readable, practical and well-illustrated, the sixth edition of the Handbook of Kidney Transplantation has been thoroughly updated and revised to reflect the most current knowledge and practice in the field. Ideal for physicians, surgeons, fellows, and nurses who manage kidney transplant patients, it covers everything from treatment options for end-stage renal disease to transplantation, post-operative management and transplant immunology, focusing on every key aspect of the clinical practice of kidney transplantation.
 Includes new chapters on the Allocation of Deceased... View Details

Transplantation of the Liver, 3e
by Ronald W. Busuttil MD PhD (Author), Goran B. Klintmalm MD PhD (Author)

Drs. Busuttil and Klintmalm present Transplantation of the Liver, 3rd Edition, which has been thoroughly revised to offer you the latest protocols, surgical approaches, and techniques used in this challenging procedure. Encompassing today's expert knowledge in the field, this medical reference book is an ideal single source for authoritative, up-to-date guidance on every imaginable aspect of liver transplantation.

"They have, in fact, succeeded in raising the bar yet again and making their work product even better in the third edition of... View Details

Thomas' Hematopoietic Cell Transplantation, 2 Volume Set: Stem Cell Transplantation
by Stephen J. Forman (Editor), Robert S. Negrin (Editor), Joseph H. Antin (Editor), Frederick R. Appelbaum (Editor)

Fully revised for the fifth edition, this outstanding reference on bone marrow transplantation is an essential, field-leading resource. Extensive coverage of the field, from the scientific basis for stem-cell transplantation to the future direction of research Combines the knowledge and expertise of over 170 international specialists across 106 chapters Includes new chapters addressing basic science experiments in stem-cell biology, immunology, and tolerance Contains expanded content on the benefits and challenges of transplantation, and analysis of the impact of new therapies to help... View Details

Transplantation Ethics
by Robert Veatch (Author), Lainie Friedman Ross (Author)

Although the history of organ transplant has its roots in ancient Christian mythology, it is only in the past fifty years that body parts from a dead person have successfully been procured and transplanted into a living person. After fourteen years, the three main issues that Robert Veatch first outlined in his seminal study Transplantation Ethics still remain: deciding when human beings are dead; deciding when it is ethical to procure organs; and deciding how to allocate organs, once procured.

However, much has changed. Enormous strides have been made in immunosuppression.... View Details

Clinical Manual of Blood and Bone Marrow Transplantation
by Syed A. Abutalib (Editor), Parameswaran Hari (Editor)

Providing the practicing and trainee hematologist with a practical and immediately applicable compendium of answers the Clinical Manual of Blood and Bone Marrow Transplantation covers the spectrum of the hematopoietic cell transplant specialty, in particular practical issues in transplant patient care, and the set up and functioning of a transplant program.  
Supplies the practicing and trainee hematologist with a practical and immediately applicable compendium of answers to clinical questions Covers the spectrum of the hematopoietic cell transplant specialty, in particular... View Details

The Ethics of Organ Transplantation
by Steven J. Jensen (Editor)

An ever-increasing demand for organs, with over 100,000 people on waiting lists, has driven a relentless search for new sources of organs. In 1995 the American Medical Association supported taking organs from anencephalic infants, children born without brains. In 1999 the Chinese government began removing organs from members of the politically outcast religious group Falun Gong, making a lucrative profit from sales to foreigners. Recently in Belgium physicians have euthanized a patient by removing her organs.

The search for fresh organs began much earlier, in 1968, when death... View Details

Transplantation, An Issue of Anesthesiology Clinics, 1e (The Clinics: Internal Medicine)
by Aman Mahajan MD PhD (Author), Christopher Wray MD (Author)

This issue of Anesthesiology Clinics focuses on Transplantation. Editors Aman Mahajan and Christopher Wray have assembled an expert team of authors on topics such as: Immunology and Pharmacology of Transplantation; Infectious Diseases and Malignancies in Transplantation; Anesthesia Management of the Organ Donor; Transfusion Medicine and Coagulation Management in Organ Transplantation; Pediatric Transplantation; Anesthesia for Kidney and Pancreas Transplantation; Anesthesia for Heart Transplantation; Anesthesia for Lung Transplantation; Anesthesia for Liver Transplantation; Anesthesia for... View Details

Sickle Cell Disease and Hematopoietic Stem Cell Transplantation
by Emily Riehm Meier (Editor), Allistair Abraham (Editor), Ross M. Fasano (Editor)

This book provides a comprehensive, state-of-the art review of hematopoietic stem cell transplantation (HSCT) for sickle cell disease (SCD).  The book reviews new data about risk prediction for severe SCD, outlines the unique challenges of  HSCT for patients with SCD, profiles the supportive care guidelines for patients who are undergoing HSCT, highlights our current understanding of the best transfusion support for SCD patients prior to, during and after HSCT, and provides new perspectives about the ethics of HSCT for pediatric patients with SCD. Published in the last few years, several... View Details

Multiorgan Procurement for Transplantation
by Paolo Aseni (Editor), Antonino Grande (Editor), Luciano De Carlis (Editor)

This well-illustrated handbook provides answers to important questions that may arise during the retrieval of multiple organs for transplantation and offers step-by-step descriptions of current surgical techniques for procurement of the various thoracic and abdominal organs, including heart, lung, liver, intestine, pancreas, and kidney. The coverage includes detailed instruction on liver splitting techniques and on living donor liver hepatectomies and laparoscopic and robot-assisted nephrectomy for transplantation. In addition, guidance is provided on preoperative evaluation for multiorgan... View Details

Manual of Stem Cell and Bone Marrow Transplantation
by Joseph H. Antin (Author), Deborah Yolin Raley (Author)

Fully revised throughout, the second edition of Manual of Stem Cell and Bone Marrow Transplantation is based on the in-house handbook used at the world-renowned Dana-Farber Cancer Institute. It is a practical pocket manual for all members of the stem cell and bone marrow transplant team. Written by experts at Dana-Farber, the contents are handily arranged in outline format for maximum usefulness and convenience. This essential and user-friendly manual covers all aspects of the transplantation process, from stem cell processing through management of transplant-related complications. Topics... View Details

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Simple Solutions
Sometimes, the best solutions to complex problems are simple. But simple doesn't always mean easy. This hour, TED speakers describe the innovation and hard work that goes into achieving simplicity. Guests include designer Mileha Soneji, chef Sam Kass, sleep researcher Wendy Troxel, public health advocate Myriam Sidibe, and engineer Amos Winter.
Now Playing: Science for the People

#448 Pavlov (Rebroadcast)
This week, we're learning about the life and work of a groundbreaking physiologist whose work on learning and instinct is familiar worldwide, and almost universally misunderstood. We'll spend the hour with Daniel Todes, Ph.D, Professor of History of Medicine at The Johns Hopkins University, discussing his book "Ivan Pavlov: A Russian Life in Science."