ABSTRACT
Roberto Toni,a,b,k Elena Bassi,a Fulvio Barbaro,a Nicoletta Zini,c Alessandra Zamparelli,a Marco Alfieri,a Davide Dallatana,a Salvatore Mosca,a Claudia della Casa,a Cecilia Gnocchi,d Giuseppe Lippi,e Giulia Spaletta,f Elena Bassoli,g Lucia Denti,g Andrea Gatto,g Francesca Ricci,h Pier Luigi Tazzari,h Annapaola Parrilli,i Milena Fini,i Monica Sandri,j Simone Sprio,j and Anna TampierijaDepartment of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T), Laboratory of Regenerative Morphology and Bioartificial Structures/S.Bi.Bi.T. Museum, Section of Human Anatomy, University of Parma School of Medicine, Parma, ItalybUnit of Anthropometry and Constitutional Medicine, Center for Sport and Exercise Medicine, University of Parma School of Medicine, Parma, ItalycCNR-National Research Council of Italy, IGM, IOR, Bologna, ItalydLaboratory of Hematochemistry, Maggiore Hospital-Parma, ItalyeClinical Biochemistry Section, Department of Biomedical and Motor Neurological Sciences, University of Verona, Verona, ItalyfDepartment of Mathematics, University of Bologna, Bologna, ItalygDepartment of Engineering “Enzo Ferrari” (DIEF), University of Modena and Reggio Emilia, Modena, ItalyhBlood Transfusion Medicine, Saint Orsola-Malpighi Hospital, Bologna, ItalyiLaboratories of Preclinical and Surgical Studies, and Biocompatibility, Innovative Technologies, and Advanced Therapies (BITTA), Rizzoli Research Innovation Technology (RIT), IOR, Bologna, ItalyjISTEC-CNR, Faenza, ItalykDepartment of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center-Tufts University School of Medicine, Boston, MA, USA
Bioartificial endocrine organs comprise classical endocrine glands, and soft (parenchyma) and hard (mineralized) tissue organs involved in endocrine-metabolic regulation. These bioconstructs are one of the newest promises of regenerative medicine, but their bioengineering “on the laboratory bench” and thus, outside the living body (i.e. ex situ) remains a substantial challenge [1, 2]. Based on current concepts [3-5], bioartificial endocrine organs can be engineered ex situ using macroscopic, three-dimensional (3D) scaffolds that mimic the 3D architecture of the native, organ stromal support (here coined organomorphism) reproduced with either natural or synthetic biomaterials. Once pluripotent stem cells, tissue-committed progenitors, and differentiated primary cells are seeded and co-cultured with the organomorphic scaffold, their self-assembly is expected up to the formation of a 3D macroscopic, functional and immuno-tolerant organ, replicating the native one. However, 3D systems exhibiting appropriate flow and trophic performance (bioreactor) are required to maximize homing, survival, growth, and differentiation/transdifferentiation of seeded elements [3, 6, 7]. Embryonic stem cells (ESCs) and induced pluripotent stem cells are also raising hopes as valuable sources to bioengineer human bioartificial viscera [8, 9]; thus, in the near future they may become another option to reconstruct ex situ bioartificial endocrine organs.
