title: Design and validation of a clinical-scale bioreactor for long-term isolated lung culture.
abstract: The primary treatment for end-stage lung disease is lung transplantation. However, donor organ shortage remains a major barrier for many patients. In recent years, techniques for maintaining lungs ex vivo for evaluation and short-term (<12 h) resuscitation have come into more widespread use in an attempt to expand the donor pool. In parallel, progress in whole organ engineering has provided the potential perspective of patient derived grafts grown on demand. As both of these strategies advance to more complex interventions for lung repair and regeneration, the need for a long-term organ culture system becomes apparent. Herein we describe a novel clinical scale bioreactor capable of maintaining functional porcine and human lungs for at least 72 h in isolated lung culture (ILC). The fully automated, computer controlled, sterile, closed circuit system enables physiologic pulsatile perfusion and negative pressure ventilation, while gas exchange function, and metabolism can be evaluated. Creation of this stable, biomimetic long-term culture environment will enable advanced interventions in both donor lungs and engineered grafts of human scale.
authors.affiliation: Thoracic Surgery, Massachusetts General Hospital, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Charest
authors.affiliation: Thoracic Surgery, Massachusetts General Hospital, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Thoracic Surgery, Massachusetts General Hospital, USA.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kitano
authors.affiliation: Thoracic Surgery, Massachusetts General Hospital, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yasuda
authors.affiliation: Thoracic Surgery, Massachusetts General Hospital, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gilpin
authors.affiliation: Thoracic Surgery, Massachusetts General Hospital, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Mathisen
authors.affiliation: Thoracic Surgery, Massachusetts General Hospital, USA; Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Boston, MA, USA.
authors.forename: Harald C
authors.initials: HC
authors.lastname: Ott
mesh_terms: D000818:Animals; D019149:Bioreactors; D004867:Equipment Design; D006801:Humans; D008168:Lung / Q000502:physiology* / Q000648:ultrastructure*; D009924:Organ Culture Techniques / Q000295:instrumentation*; D009926:Organ Preservation / Q000295:instrumentation*; D010477:Perfusion / Q000295:instrumentation; D013552:Swine
keywords: Ex-vivo perfusion; Isolated lung culture; Lung preservation; Lung transplantation; Organ repair
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