title: Perfusion decellularization of whole organs.
abstract: The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo.
authors.affiliation: 1] Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3].
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Guyette
authors.affiliation: 1] Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3].
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gilpin
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Charest
authors.affiliation: 1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Surgery, Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Tapias
authors.affiliation: 1] Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Ren
authors.affiliation: 1] Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Surgery, Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA. [4] Harvard Stem Cell Institute, Boston, Massachusetts, USA.
authors.forename: Harald C
authors.initials: HC
authors.lastname: Ott
mesh_terms: D000818:Animals; D003902:Detergents; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000302:isolation & purification*; D006801:Humans; D010477:Perfusion / Q000379:methods*; D011312:Pressure; D051381:Rats; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014781:Viscera / Q000166:cytology*
chemical_list: D003902:Detergents; D016326:Extracellular Matrix Proteins