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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| Veröffentlicht in: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 2020-02, Vol.21 (3), p.1004 |
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| creator | Zubillaga, Veronica Alonso-Varona, Ana Fernandes, Susana C M Salaberria, Asier M Palomares, Teodoro |
| 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. |
| doi_str_mv | 10.3390/ijms21031004 |
| format | Article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21031004</identifier><identifier>PMID: 32028724</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adipose tissue ; Aggrecan ; Biocompatibility ; Biomedical materials ; Bone marrow ; Cartilage ; Cartilage (articular) ; Cartilage, Articular - cytology ; Cartilage, Articular - metabolism ; Cell Differentiation ; Cells, Cultured ; Chitin ; Chitin - chemistry ; Chitosan ; Chitosan - chemistry ; Chondrocytes - cytology ; Chondrocytes - metabolism ; Chondrogenesis ; Collagen ; Collagen (type I) ; Collagen (type II) ; Degeneration ; Differentiation (biology) ; Extracellular matrix ; Genipin ; Glycosaminoglycans ; Humans ; Hypoxia ; Hypoxia-inducible factor 1a ; Hypoxia-inducible factors ; Mechanical properties ; Mesenchymal stem cells ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - metabolism ; Nanocrystals ; Nanoparticles - chemistry ; Scaffolds ; Spheroids ; Spheroids, Cellular - cytology ; Spheroids, Cellular - metabolism ; Stem cells ; Tissue engineering ; Tissue Engineering - methods ; Tissue Scaffolds - chemistry ; Wound healing</subject><ispartof>INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020-02, Vol.21 (3), p.1004</ispartof><rights>2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 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These findings highlight the potential use of such templates in cartilage tissue engineering.</description><subject>Adipose tissue</subject><subject>Aggrecan</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Bone marrow</subject><subject>Cartilage</subject><subject>Cartilage (articular)</subject><subject>Cartilage, Articular - cytology</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Chitin</subject><subject>Chitin - chemistry</subject><subject>Chitosan</subject><subject>Chitosan - chemistry</subject><subject>Chondrocytes - cytology</subject><subject>Chondrocytes - metabolism</subject><subject>Chondrogenesis</subject><subject>Collagen</subject><subject>Collagen (type I)</subject><subject>Collagen (type II)</subject><subject>Degeneration</subject><subject>Differentiation (biology)</subject><subject>Extracellular matrix</subject><subject>Genipin</subject><subject>Glycosaminoglycans</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-inducible factor 1a</subject><subject>Hypoxia-inducible factors</subject><subject>Mechanical properties</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Nanocrystals</subject><subject>Nanoparticles - chemistry</subject><subject>Scaffolds</subject><subject>Spheroids</subject><subject>Spheroids, Cellular - cytology</subject><subject>Spheroids, Cellular - metabolism</subject><subject>Stem cells</subject><subject>Tissue engineering</subject><subject>Tissue Engineering - methods</subject><subject>Tissue Scaffolds - chemistry</subject><subject>Wound healing</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>D8T</sourceid><recordid>eNpVkk1v1DAQhi0EoqVw44wscSXUX3GSC1KVFopUoBLlbM0mk42XxA52Utg_xW_Eq12q7cUeeZ55Z8YzhLzm7L2UFTu3mzEKziRnTD0hp1wJkTGmi6dH9gl5EeOGMSFFXj0nJ1IwURZCnZK_F62dfMTsEoO9x5Z-wYiu6bcjDPT7jCOtcRho3XvXBh-nHoO3baT1MsxLSLx19Ho7-T8WKLiWApWX9NYHvySmt7OP4M53RuK-gvNN2MZ5J91A1_khBcQUczvA3Pkw0nTQGsJsB1gjvbMxLkiv3No6TPW59UvyrIMh4qvDfUZ-fLy6q6-zm2-fPtcXN1mTcz1nbblqu0p3qeO8UQgahEIJ3UpwbDRXbZlXAFKuMH0hl11eYaVKxBwLVQreyDOS7XXjb5yWlZmCHSFsjQdrDk8_k4VGFVKXLPEf9nzyjNg26OYAw6Owxx5ne7P296ZgshBVkQTeHgSC_7VgnM3GL8GlHo3IVakrrYVO1Ls91aRZxIDdQwbOzG4bzPE2JPzNcVUP8P_xy3_8kbVC</recordid><startdate>20200203</startdate><enddate>20200203</enddate><creator>Zubillaga, Veronica</creator><creator>Alonso-Varona, Ana</creator><creator>Fernandes, Susana C M</creator><creator>Salaberria, Asier M</creator><creator>Palomares, Teodoro</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-0601-9322</orcidid></search><sort><creationdate>20200203</creationdate><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><author>Zubillaga, Veronica ; Alonso-Varona, Ana ; Fernandes, Susana C M ; Salaberria, Asier M ; Palomares, Teodoro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c516t-d8bdf96f0025c4ea6a24e3afb21ec614d859aa33be33913f59e948ee5e74821c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adipose tissue</topic><topic>Aggrecan</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>Bone marrow</topic><topic>Cartilage</topic><topic>Cartilage (articular)</topic><topic>Cartilage, Articular - 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32028724</pmid><doi>10.3390/ijms21031004</doi><orcidid>https://orcid.org/0000-0002-0601-9322</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SWEPUB Freely available online |
| subjects | Adipose tissue Aggrecan Biocompatibility Biomedical materials Bone marrow Cartilage Cartilage (articular) Cartilage, Articular - cytology Cartilage, Articular - metabolism Cell Differentiation Cells, Cultured Chitin Chitin - chemistry Chitosan Chitosan - chemistry Chondrocytes - cytology Chondrocytes - metabolism Chondrogenesis Collagen Collagen (type I) Collagen (type II) Degeneration Differentiation (biology) Extracellular matrix Genipin Glycosaminoglycans Humans Hypoxia Hypoxia-inducible factor 1a Hypoxia-inducible factors Mechanical properties Mesenchymal stem cells Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - metabolism Nanocrystals Nanoparticles - chemistry Scaffolds Spheroids Spheroids, Cellular - cytology Spheroids, Cellular - metabolism Stem cells Tissue engineering Tissue Engineering - methods Tissue Scaffolds - chemistry Wound healing |
| 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 |
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