Organ Donation for IPF Research: A Pulmonary Perspective

The Division of Pulmonary and Critical Care Medicine is actively involved with the Gift of Life Michigan organ procurement organization to perform pulmonary research.

Our Division faculty use tissue from normal and diseased lungs to perform research in COPD, pulmonary fibrosis, acute lung injury, and the lung microbiome.  The leader in acquisition and dissemination of tissue, bronchoalveolar lavage fluid and primary lung cells and matrix is Dr. Eric White, Associate Professor of Internal Medicine.

Dr. White and his lab staff acquires lungs 24/7 from operating rooms in southeastern Michigan and preserves and disseminates tissues to labs across our institution and around the world for pulmonary research.   To date they have acquired 30 diseased lungs and 50 normal lungs for use in research.  Dr. White, his staff and postdocs are on call to receive lungs from Southeastern Michigan hospitals (Henry Ford, St. Johns, Detroit Receiving and our own UMHS OR, to name a few) upon a call from Gift of Life.  Teams of physicians and scientists wait patiently for lungs, kidneys, liver, heart for either transplant or for scientific study, depending on the condition and viability of the tissue when Gift of Life calls.

Dr. White bringing inflated lungs back to the lab for sourcing to the various research programs. Pulmonary research is dependent upon these organ donations.

The White lab lung courier sometimes has to take samples right away in the OR for TEM or SEM studies so the tissue can be protected from degradation.  They prepare snap frozen lung, slices of acellular matrix and sometimes whole lung for scientific experiments or for sending to their collaborators. 

Yale, University of California at San Francisco, UCLA, Georgia Tech and Brown work with the White lab to acquire tissue for either their unique experiments or through consortium agreements. 

Organ donations typically start late at night or in the early-morning hours to avoid using operating rooms during scheduled times, and on occasion procurement may be delayed because of emergent cases. Research lungs are procured after all organs being used for transplant have been recovered. Recovered lungs typically arrive in the White lab between 3 and 6 am, and the process of isolating cells, collecting samples, and beginning decellularization, starts shortly thereafter. Isolation of the alveolar epithelial cells, vascular endothelium, and fibroblasts may take up to 10 hours, while processing the tissues for the various experiments may require 2 or 3 additional personnel to ensure everything is collected in a timely fashion. 

The right lung has 3 lobes; the left lung has 2.

Research in COPD, asthma, the lung microbiome, and pulmonary fibrosis is served by lung acquisition.  Normal and diseased lung samples are evaluated at the gene, protein, and structural level to provide clues to human lung pathologic processes. These observations serve as a springboard for the mechanistic work being done in the lab to unravel pathogenesis of idiopathic pulmonary fibrosis, a rare but progressive form of lung scarring that leads to chronic respiratory failure and death. Most recently, the White lab has developed methods to decellularize the human lungs, using them as a scaffold to explore the possibilities of human lung regeneration. Using a bioreactor that allows for vascular perfusion and mechanical ventilation, this lab has successfully re-introduced airway epithelium into acellular human lung and is exploring the mechanisms by which airway re-epithelialization might be achieved. The broad access to human lung tissue from donors expands our understanding of human lung diseases. The White lab hopes to identify keys to combat serious pulmonary disorders.

The White lab’s intensity of effort has resulted in a unique role for his lung procurement program in pulmonary research throughout the country. This is the single human lung repository in existence that banks samples for a continuum of study of incurable human lung disorders (COPD, pulmonary fibrosis, asthma, lung microbiome, acute lung injury, etc.). This archive is a treasure for scientists to draw from in studying the human lung.  At the 2014 American Thoracic International Conference, Dr. White’s paper

 

Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. by Booth AJ, Hadley R, Cornett AM, Dreffs AA, Matthes SA, Tsui JL, Weiss K, Horowitz JC, Fiore VF, Barker TH, Moore BB, Martinez FJ, Niklason LE, White ES.  Am J Respir Crit Care Med. 2012 Nov 1;186(9):866-76.

was cited as pioneering work in culturing cells and commended as a vanguard in the field.  Looking at Merriam Webster for definition of vanguard they cite: 

van·guard  noun \ˈvan-ˌgärd also ˈvaŋ-\:  the group of people who are the leaders of an action or movement in society, politics, art, etc.

the vanguard : the soldiers, ships, etc., that are at the front of a fighting force that is moving forward

 

Both these definitions fit the extreme team that comprises Dr. Eric S. White’s Lung Procurement Program!

Ryan Hadley, M.D., Rachel Dyal, Ashley Cornett, Emily Speelmon, M.D., Ph.D.,  Eric S. White, M.D., Stephanie Matthes, Ph.D.

 

 

Interest in learning about this program?  You can call the lab @ (734) 763-4359 in MSRB III.