title: Orthotopic transplantation of a tissue engineered diaphragm in rats.
abstract: The currently available surgical options to repair the diaphragm are associated with significant risks of defect recurrence, lack of growth potential and restored functionality. A tissue engineered diaphragm has the potential to improve surgical outcomes for patients with congenital or acquired disorders. Here we show that decellularized diaphragmatic tissue reseeded with bone marrow mesenchymal stromal cells (BM-MSCs) facilitates in situ regeneration of functional tissue. A novel bioreactor, using simultaneous perfusion and agitation, was used to rapidly decellularize rat diaphragms. The scaffolds retained architecture and mechanical properties and supported cell adhesion, proliferation and differentiation. Biocompatibility was further confirmed in vitro and in vivo. We replaced 80% of the left hemidiaphragm with reseeded diaphragmatic scaffolds. After three weeks, transplanted animals gained 32% weight, showed myography, spirometry parameters, and histological evaluations similar to native rats. In conclusion, our study suggested that reseeded decellularized diaphragmatic tissue appears to be a promising option for patients in need of diaphragmatic reconstruction.
authors.affiliation: International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Gubareva
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Sjöqvist
authors.affiliation: International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Gilevich
authors.affiliation: International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Sotnichenko
authors.affiliation: International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kuevda
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mei Ling
authors.initials: ML
authors.lastname: Lim
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Neus
authors.initials: N
authors.lastname: Feliu
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Greg
authors.initials: G
authors.lastname: Lemon
authors.affiliation: International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Danilenko
authors.affiliation: International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Ramazan Z
authors.initials: RZ
authors.lastname: Nakokhov
authors.affiliation: International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Gumenyuk
authors.affiliation: National Research Centre "Kurchatov Institute" (NRC "Kurchatov Institute") Laboratory of Polymer Materials, Moscow, Russian Federation.
authors.forename: Timofei E
authors.initials: TE
authors.lastname: Grigoriev
authors.affiliation: National Research Centre "Kurchatov Institute" (NRC "Kurchatov Institute") Laboratory of Polymer Materials, Moscow, Russian Federation.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Krasheninnikov
authors.affiliation: Department of Human Physiology, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Pokhotko
authors.affiliation: Common Use Center for Diagnostics of Nanomaterials, Structure and Properties, Kuban State University, Krasnodar, Russian Federation.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Basov
authors.affiliation: Common Use Center for Diagnostics of Nanomaterials, Structure and Properties, Kuban State University, Krasnodar, Russian Federation.
authors.forename: Stepan S
authors.initials: SS
authors.lastname: Dzhimak
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Gustafsson
authors.affiliation: College of Medicine, University of Illinois, Chicago, IL, United States.
authors.forename: Geoanna
authors.initials: G
authors.lastname: Bautista
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Antonio
authors.initials: A
authors.lastname: Beltrán Rodríguez
authors.affiliation: Department of Human Physiology, Kuban State Medical University, Krasnodar, Russian Federation.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Pokrovsky
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Philipp
authors.initials: P
authors.lastname: Jungebluth
authors.affiliation: National Research Centre "Kurchatov Institute" (NRC "Kurchatov Institute") Laboratory of Polymer Materials, Moscow, Russian Federation.
authors.forename: Sergei N
authors.initials: SN
authors.lastname: Chvalun
authors.affiliation: Department of Surgery, College of Medicine, University of Illinois, Chicago, IL, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Holterman
authors.affiliation: Texas Heart Institute, Center for Regenerative Medicine, Houston, TX, United States.
authors.forename: Doris A
authors.initials: DA
authors.lastname: Taylor
authors.affiliation: International Research, Clinical and Education Center of Regenerative Medicine, Kuban State Medical University, Krasnodar, Russian Federation; Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden. Electronic address: paolo.macchiarini@ki.se.
authors.forename: Paolo
authors.initials: P
authors.lastname: Macchiarini
mesh_terms: D020341:Absorbable Implants; D064591:Allografts; D000818:Animals; D019149:Bioreactors; D002448:Cell Adhesion; D002454:Cell Differentiation; D003964:Diaphragm / Q000098:blood supply / Q000000981:diagnostic imaging / Q000276:immunology / Q000637:transplantation*; D004576:Electromyography; D006085:Graft Survival; D065630:Hernias, Diaphragmatic, Congenital; D008264:Macrophages / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D018919:Neovascularization, Physiologic; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds; D016042:Transplantation, Heterotopic; D019737:Transplants / Q000098:blood supply / Q000276:immunology / Q000502:physiology; D014945:Wound Healing
keywords: Biocompatibility; Diaphragm; Scaffolds; Tissue engineering; Transplantation