The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement

The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement

Authors

  • Roberto Toni Departments of Parma; Departments of Scientific Foundation and Clinic “G. B. Morgagni”, Catania; Academy of Sciences, Bologna, Italy; Departments of Medicine, Divisions of Endocrinology, Sloan-Kettering Cancer Center, New York
  • Claudia Della Casa Departments of Parma
  • Giulia Spaletta Departments of Human Anatomy, Mathematics-CIRAM-Engineering, Bologna
  • Giacomo Marchetti Departments of Human Anatomy, Mathematics-CIRAM-Engineering, Bologna
  • Perseo Mazzoni Departments of Human Anatomy, Mathematics-CIRAM-Engineering, Bologna
  • Monica Bodria Departments of Parma
  • Simone Ravera Departments of Parma
  • Davide Dallatana Departments of Parma
  • Sergio Castorina Departments of Human Anatomy, Scientific Foundation and Clinic “G. B. Morgagni”, Catania
  • Vincenzo Riccioli Departments of Scientific Foundation and Clinic “G. B. Morgagni”
  • Emilio Giovanni Castorina Departments of Scientific Foundation and Clinic “G. B. Morgagni”
  • Salvatore Antoci Departments of Scientific Foundation and Clinic “G. B. Morgagni”
  • Enrico Campanile Departments of Scientific Foundation and Clinic “G. B. Morgagni”
  • Gabriella Scalise Departments of Nuclear Medicine and Sanitary Physics, Universities of Maggiore Hospital, Parma
  • Raffaella Rossi Departments of Nuclear Medicine and Sanitary Physics, Universities of Maggiore Hospital, Parma
  • Giorgio Ugolotti Departments of Nuclear Medicine and Sanitary Physics, Universities of Maggiore Hospital, Parma
  • Andrew Martorella Departments of Departments of Medicine, Divisions of Endocrinology, Sloan-Kettering Cancer Center, New York
  • Elio Roti Departments of Mathematics-CIRAM-Engineering, Bologna
  • Fiorella Sgallari Departments of Human Anatomy, Mathematics-CIRAM-Engineering, Bologna
  • Aldo Pinchera Departments of Endocrinology, Pisa

Keywords:

Bioengineering, biomaterial, biotechnology, scaffold, thyroid, endothelial cell, stroma, thyroid vessel, transplantation, thyroid papillary cancer

Abstract

A new concept for ex situ endocrine organ bioengineering is presented, focused on the realization of a human bioartificial thyroid gland. It is based on the theoretical assumption and experimental evidence that symmetries in geometrical coordinates of the thyroid tissue remain invariant with respect to developmental, physiological or pathophysiological transformations occuring in the gland architecture. This topological arrangement is dependent upon physical connections established between cells, cell adhesion molecules and extracellular matrix, leading to the view that the thyroid parenchyma behaves like a deformable “putty”, moulded onto an elastic stromal/vascular scaffold (SVS) dictating the final morphology of the gland. In particular, we have raised the idea that the geometry of the SVS per se provides pivotal epigenetic information to address the genetically-programmed, thyrocyte and endothelial/vascular proliferation and differentiation towards a functionally mature gland, making organ form a pre-requirement for organ function. A number of experimental approaches are explored to obtain a reliable replica of a human thyroid SVS, and an informatic simulation is designed based on fractal growth of the thyroid intraparenchymal arterial tree. Various tissue-compatible and degradable synthetic or biomimetic polymers are discussed to act as a template of the thyroid SVS, onto which to co-seed autologous human thyrocyte (TPC) and endothelial/vascular (EVPC) progenitor cells. Harvest and expansion of both TPC and EVPC in primary culture are considered, with specific attention to the selection of normal thyrocytes growing at a satisfactory rate to colonize the synthetic matrix. In addition, both in vitro and in vivo techniques to authenticate TPC and EVPC lineage differentiation are reviewed, including immunocytochemistry, reverse trascriptase-polymerase chain reaction, flow cytomery and proteomics. Finally, analysis of viability of the thyroid construct following implantation in animal hosts is proposed, with the intent to obtain a bioartificial thyroid gland morphologically and functionally adequate for transplantation. We believe that the biotechnological scenario proposed herein may provide a template to construct other, more complex and clinically-relevant bioartificial endocrine organs ex situ, such as human pancreatic islets and the liver, and perhaps a new approach to brain bioengineering.

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Published

01-03-2007

How to Cite

1.
The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement. Acta Biomed [Internet]. 2007 Mar. 1 [cited 2024 Apr. 24];78(1Suppl):129-55. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/4617