Ex situ bioengineering of bioartificial endocrine glands: A new frontier in regenerative medicine of soft tissue organs

Ex situ bioengineering is one of the most promising perspectives in the field of regenerative medicineallowing for organ reconstruction outside the living body; i.e. on the laboratory bench. A number of hollowviscera of the cardiovascular, respiratory, genitourinary, and digestive systems have been successfullybioengineered ex situ, exploiting biocompatible scaffolds with a 3D morphology that recapitulates thatof the native organ (organomorphic scaffold). In contrast, bioengineering of entire soft tissue organsand, in particular endocrine glands still remains a substantial challenge. Primary reasons are that noorganomorphic scaffolding for endocrine viscera have as yet been entirely assembled using biocompatiblematerials, nor is there a bioreactor performance capable of supporting growth within the thicknessrange of the regenerating cell mass which has proven to be reliable enough to ensure formation of a completemacroscopic gland ex situ. Current technical options for reconstruction of endocrine viscera includeeither biocompatible 3D reticular scaffolds lacking any organomorphic geometry, or allogenic/xenogenicacellular 3D matrices derived from a gland similar to that to be bioengineered, eventually recellularizedby autologous/heterologous cells. In 2007, our group designed, using biocompatible material, anorganomorphic scaffold–bioreactor unit for bioengineering ex situ the human thyroid gland, chosen as amodel for its simple anatomical organization (repetitive follicular cavities). This unit reproduces both the3D native geometry of the human thyroid stromal/vascular scaffold, and the natural thyrocyte/vascularinterface. It is now under intense investigation as an experimental tool to test cellular 3D auto-assemblyof thyroid tissue and its related vascular system up to the ex situ generation of a 3D macroscopic thyroidgland. We believe that these studies will lay the groundwork for a new concept in regenerative medicineof soft tissue and endocrine organs; i.e. that the organomorphism of a biocompatible scaffold–bioreactorcomplex is essential to both the 3D organization of seeded stem cells/precursor cells and their phenotypicfate as glandular/parenchymal/vascular elements, eventually leading to a physiologically competent andimmuno-tolerant bioconstruct, macroscopically suitable for transplantation and clinical applications.