title: Ex situ bioengineering of bioartificial endocrine glands: a new frontier in regenerative medicine of soft tissue organs.
abstract: Ex situ bioengineering is one of the most promising perspectives in the field of regenerative medicine allowing for organ reconstruction outside the living body; i.e. on the laboratory bench. A number of hollow viscera of the cardiovascular, respiratory, genitourinary, and digestive systems have been successfully bioengineered ex situ, exploiting biocompatible scaffolds with a 3D morphology that recapitulates that of the native organ (organomorphic scaffold). In contrast, bioengineering of entire soft tissue organs and, in particular endocrine glands still remains a substantial challenge. Primary reasons are that no organomorphic scaffolding for endocrine viscera have as yet been entirely assembled using biocompatible materials, nor is there a bioreactor performance capable of supporting growth within the thickness range of the regenerating cell mass which has proven to be reliable enough to ensure formation of a complete macroscopic gland ex situ. Current technical options for reconstruction of endocrine viscera include either biocompatible 3D reticular scaffolds lacking any organomorphic geometry, or allogenic/xenogenic acellular 3D matrices derived from a gland similar to that to be bioengineered, eventually recellularized by autologous/heterologous cells. In 2007, our group designed, using biocompatible material, an organomorphic scaffold-bioreactor unit for bioengineering ex situ the human thyroid gland, chosen as a model for its simple anatomical organization (repetitive follicular cavities). This unit reproduces both the 3D native geometry of the human thyroid stromal/vascular scaffold, and the natural thyrocyte/vascular interface. It is now under intense investigation as an experimental tool to test cellular 3D auto-assembly of thyroid tissue and its related vascular system up to the ex situ generation of a 3D macroscopic thyroid gland. We believe that these studies will lay the groundwork for a new concept in regenerative medicine of soft tissue and endocrine organs; i.e. that the organomorphism of a biocompatible scaffold-bioreactor complex is essential to both the 3D organization of seeded stem cells/precursor cells and their phenotypic fate as glandular/parenchymal/vascular elements, eventually leading to a physiologically competent and immuno-tolerant bioconstruct, macroscopically suitable for transplantation and clinical applications.
authors.affiliation: Department of Human Anatomy, Pharmacology and Forensic Medicine, Laboratory of Regenerative Morphology and Bioartificial Structures, University of Parma, Italy. roberto.toni@unipr.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Toni
authors.forename: Anna
authors.initials: A
authors.lastname: Tampieri
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zini
authors.forename: Valentina
authors.initials: V
authors.lastname: Strusi
authors.forename: Monica
authors.initials: M
authors.lastname: Sandri
authors.forename: Davide
authors.initials: D
authors.lastname: Dallatana
authors.forename: Giulia
authors.initials: G
authors.lastname: Spaletta
authors.forename: Elena
authors.initials: E
authors.lastname: Bassoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Gatto
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
mesh_terms: D000818:Animals; D021522:Bioartificial Organs / Q000639:trends; D057005:Bioengineering; D004702:Endocrine Glands / Q000502:physiology*; D006801:Humans; D044968:Regenerative Medicine / Q000639:trends