title: Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering.
abstract: Approximately 285 million people worldwide suffer from diabetes, with insulin supplementation as the most common treatment measure. Regenerative medicine approaches such as a bioengineered pancreas has been proposed as potential therapeutic alternatives. A bioengineered pancreas will benefit from the development of a bioscaffold that supports and enhances cellular function and tissue development. Perfusion-decellularized organs are a likely candidate for use in such scaffolds since they mimic compositional, architectural and biomechanical nature of a native organ. In this study, we investigate perfusion-decellularization of whole pancreas and the feasibility to recellularize the whole pancreas scaffold with pancreatic cell types. Our result demonstrates that perfusion-decellularization of whole pancreas effectively removes cellular and nuclear material while retaining intricate three-dimensional microarchitecture with perfusable vasculature and ductal network and crucial extracellular matrix (ECM) components. To mimic pancreatic cell composition, we recellularized the whole pancreas scaffold with acinar and beta cell lines and cultured up to 5 days. Our result shows successful cellular engraftment within the decellularized pancreas, and the resulting graft gave rise to strong up-regulation of insulin gene expression. These findings support biological utility of whole pancreas ECM as a biomaterials scaffold for supporting and enhancing pancreatic cell functionality and represent a step toward bioengineered pancreas using regenerative medicine approaches.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, PA, USA.
authors.forename: Saik-Kia
authors.initials: SK
authors.lastname: Goh
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bertera
authors.forename: Phillip
authors.initials: P
authors.lastname: Olsen
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Candiello
authors.forename: Willi
authors.initials: W
authors.lastname: Halfter
authors.forename: Guy
authors.initials: G
authors.lastname: Uechi
authors.forename: Manimalha
authors.initials: M
authors.lastname: Balasubramani
authors.forename: Scott A
authors.initials: SA
authors.lastname: Johnson
authors.forename: Brian M
authors.initials: BM
authors.lastname: Sicari
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kollar
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Badylak
authors.forename: Ipsita
authors.initials: I
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010179:Pancreas / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*