Original Pre-Clinical SciencePerfusion decellularization of human and porcine lungs: Bringing the matrix to clinical scale
Section snippets
Whole-organ perfusion decellularization
Animal organs were harvested in accordance with approved animal protocols and institutional guidelines. Outbred Sprague-Dawley rats (150–200 g, Charles River Laboratories, Inc, Wilmington, MA) were used throughout. Porcine lungs were harvested in-house from Yorkshire swine (40–200 kg) being otherwise used for experiments not involving the chest cavity. Rat donors were pre-treated with a dose of heparin (2.0 U/g of body weight) into the inferior vena cava. Porcine donors were not pre-treated
Results
We first aimed to analyze 3 published decellularization protocols for rat lung4, 5, 6 to determine the most suitable methods for subsequent up-scaling. A perfusion-based decellularization method was adopted for each protocol. The specific protocol details are outlined in the Methods and Supplemental Figure 1 (available in the online version of this article at jhltonline.org).
Histologic analysis of rat lungs decellularized by each protocol revealed equivalent removal of intracellular and nuclear
Discussion
More than 1,700 Americans are in need of a donor lung,1 with limited or no available alternative therapies.19 Waiting list mortality rates for lung candidates continue to rise, reported at 15.7/100 waiting list-years in 2011.20 In addition, only 21.0% of potential donor lungs are used for transplantation,20 further highlighting the shortage of adequate organs. A 50% probability of graft failure and more than 40% probability of death at 5 years after transplant remain clinical realities lung
Disclosure statement
This study was supported by the United Therapeutics Corporation and the National Institutes of Health (NIH) Director’s New Innovator Award (DP2-OD008749-01).
This work was presented at the Thirty-third Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation, Montreal, Québec, Canada, April 24–27, 2013.
HC Ott is founder and stockholder of IVIVA Medical Inc. This relationship did not influence design, execution, and/or interpretation of the present
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