Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study
Marta Anna Szychlinska,
Giovanna Calabrese,
Silvia Ravalli,
Nunziatina Laura Parrinello,
Stefano Forte,
Paola Castrogiovanni,
Elisabetta Pricoco,
Rosa Imbesi,
Sergio Castorina,
Rosalia Leonardi,
Michelino Di Rosa,
Giuseppe Musumeci
Affiliations
Marta Anna Szychlinska
Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy
Giovanna Calabrese
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Silvia Ravalli
Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy
Nunziatina Laura Parrinello
Division of Hematology, AOU “Policlinico-Vittorio Emanuele”, 95125 Catania, Italy
Stefano Forte
IOM Ricerca, 95029 Viagrande, Italy
Paola Castrogiovanni
Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy
Elisabetta Pricoco
Department of Medical and Surgical Sciences and Advanced Technologies, Anatomic Pathology Section, School of Medicine, University of Catania, 95124 Catania, Italy
Rosa Imbesi
Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy
Sergio Castorina
Department of Medical, Surgical and Advanced Technological Sciences “G.F. Ingrassia”, University of Catania, 95124 Catania, Italy
Rosalia Leonardi
Department of General Surgery and Medical-Surgical Specialties, University of Catania, 95124 Catania, Italy
Michelino Di Rosa
Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy
Giuseppe Musumeci
Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy
Stem cell therapy and tissue engineering represent a promising approach for cartilage regeneration. However, they present limits in terms of mechanical properties and premature de-differentiation of engineered cartilage. Cycloastragenol (CAG), a triterpenoid saponin compound and a hydrolysis product of the main ingredient in Astragalus membranaceous, has been explored for cartilage regeneration. The aim of this study was to investigate CAG’s ability to promote cell proliferation, maintain cells in their stable active phenotype, and support the production of cartilaginous extracellular matrix (ECM) in human adipose-derived mesenchymal stem cells (hAMSCs) in up to 28 days of three-dimensional (3D) chondrogenic culture. The hAMSC pellets were cultured in chondrogenic medium (CM) and in CM supplemented with CAG (CAG−CM) for 7, 14, 21, and 28 days. At each time-point, the pellets were harvested for histological (hematoxylin and eosin (H&E)), histochemical (Alcian-Blue) and immunohistochemical analysis (Type I, II, and X collagen, aggrecan, SOX9, lubricin). After excluding CAG’s cytotoxicity (MTT Assay), improved cell condensation, higher glycosaminoglycans (sGAG) content, and increased cell proliferation have been detected in CAG−CM pellets until 28 days of culture. Overall, CAG improved the chondrogenic differentiation of hAMSCs, maintaining stable the active chondrocyte phenotype in up to 28 days of 3D in vitro chondrogenic culture. It is proposed that CAG might have a beneficial impact on cartilage regeneration approaches.
