Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering
Articular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristic...
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doaj-657a28d3f2db4b20ab882aff157dcba32020-11-25T01:12:58ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-02-01213100410.3390/ijms21031004ijms21031004Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue EngineeringVeronica Zubillaga0Ana Alonso-Varona1Susana C. M. Fernandes2Asier M. Salaberria3Teodoro Palomares4Department of Cell Biology and Histology, Faculty of Medicine and Nursey, University of the Basque Country (UPV/EHU), B Sarriena s/n, 48940 Leioa, SpainDepartment of Cell Biology and Histology, Faculty of Medicine and Nursey, University of the Basque Country (UPV/EHU), B Sarriena s/n, 48940 Leioa, SpainInstitute of Analytical Sciences and Physico-chemistry for the Environment and Materials, University of Pau and Pays Adour, E2S UPPA, CNRS, 64600 Anglet, FranceBiorefinery Processes Research Group, Department of Chemical and Environmental Engineering, Polytechnic School, University of the Basque Country (UPV/EHU), Pza. Europa 1, 20018 Donostia-San Sebastian, SpainDepartment of Surgery, Radiology and Physic Medicine, Faculty of Medicine, University of the Basque Country (UPV/EHU), B Sarriena, s/n, 48940 Leioa, SpainArticular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristics of the cartilaginous matrix, as well as the avascular nature of cartilage and its cells’ peculiar arrangement in isogenic groups. Keeping these factors in mind, we have designed a 3D porous scaffold based on genipin-crosslinked chitosan/chitin nanocrystals for spheroid chondral differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) induced in hypoxic conditions. First, we demonstrated that, under low oxygen conditions, the chondrospheroids obtained express cartilage-specific markers including collagen type II (COL2A1) and aggrecan, lacking expression of osteogenic differentiation marker collagen type I (COL1A2). These results were associated with an increased expression of hypoxia-inducible factor 1α, which positively directs COL2A1 and aggrecan expression. Finally, we determined the most suitable chondrogenic differentiation pattern when hASC spheroids were seeded in the 3D porous scaffold under hypoxia and obtained a chondral extracellular matrix with a high sulphated glycosaminoglycan content, which is characteristic of articular cartilage. These findings highlight the potential use of such templates in cartilage tissue engineering.https://www.mdpi.com/1422-0067/21/3/1004cartilage tissue engineeringadipose tissue-derived mesenchymal stem cell spheroidshypoxia3d porous chitosan/chitin nanocrystal scaffold |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Veronica Zubillaga Ana Alonso-Varona Susana C. M. Fernandes Asier M. Salaberria Teodoro Palomares |
spellingShingle |
Veronica Zubillaga Ana Alonso-Varona Susana C. M. Fernandes Asier M. Salaberria Teodoro Palomares Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering International Journal of Molecular Sciences cartilage tissue engineering adipose tissue-derived mesenchymal stem cell spheroids hypoxia 3d porous chitosan/chitin nanocrystal scaffold |
author_facet |
Veronica Zubillaga Ana Alonso-Varona Susana C. M. Fernandes Asier M. Salaberria Teodoro Palomares |
author_sort |
Veronica Zubillaga |
title |
Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering |
title_short |
Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering |
title_full |
Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering |
title_fullStr |
Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering |
title_full_unstemmed |
Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering |
title_sort |
adipose-derived mesenchymal stem cell chondrospheroids cultured in hypoxia and a 3d porous chitosan/chitin nanocrystal scaffold as a platform for cartilage tissue engineering |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2020-02-01 |
description |
Articular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristics of the cartilaginous matrix, as well as the avascular nature of cartilage and its cells’ peculiar arrangement in isogenic groups. Keeping these factors in mind, we have designed a 3D porous scaffold based on genipin-crosslinked chitosan/chitin nanocrystals for spheroid chondral differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) induced in hypoxic conditions. First, we demonstrated that, under low oxygen conditions, the chondrospheroids obtained express cartilage-specific markers including collagen type II (COL2A1) and aggrecan, lacking expression of osteogenic differentiation marker collagen type I (COL1A2). These results were associated with an increased expression of hypoxia-inducible factor 1α, which positively directs COL2A1 and aggrecan expression. Finally, we determined the most suitable chondrogenic differentiation pattern when hASC spheroids were seeded in the 3D porous scaffold under hypoxia and obtained a chondral extracellular matrix with a high sulphated glycosaminoglycan content, which is characteristic of articular cartilage. These findings highlight the potential use of such templates in cartilage tissue engineering. |
topic |
cartilage tissue engineering adipose tissue-derived mesenchymal stem cell spheroids hypoxia 3d porous chitosan/chitin nanocrystal scaffold |
url |
https://www.mdpi.com/1422-0067/21/3/1004 |
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