Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model
Abstract While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely un...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-11-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202103320 |
| _version_ | 1818434244083449856 |
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| author | Gabriella C. J. Lindberg Xiaolin Cui Mitchell Durham Laura Veenendaal Benjamin S. Schon Gary J. Hooper Khoon S. Lim Tim B. F. Woodfield |
| author_facet | Gabriella C. J. Lindberg Xiaolin Cui Mitchell Durham Laura Veenendaal Benjamin S. Schon Gary J. Hooper Khoon S. Lim Tim B. F. Woodfield |
| author_sort | Gabriella C. J. Lindberg |
| collection | DOAJ |
| description | Abstract While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D‐bioassembly platform is introduced to primarily study fusion of cartilage–cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D‐bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type‐II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D‐model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high‐throughput 3D‐bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis. |
| first_indexed | 2024-12-14T16:33:54Z |
| format | Article |
| id | doaj.art-87d9dbf986684de386293a43cd8fa3b3 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-14T16:33:54Z |
| publishDate | 2021-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-87d9dbf986684de386293a43cd8fa3b32022-12-21T22:54:32ZengWileyAdvanced Science2198-38442021-11-01822n/an/a10.1002/advs.202103320Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly ModelGabriella C. J. Lindberg0Xiaolin Cui1Mitchell Durham2Laura Veenendaal3Benjamin S. Schon4Gary J. Hooper5Khoon S. Lim6Tim B. F. Woodfield7Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group Department of Orthopaedic Surgery University of Otago Christchurch 2 Riccarton Avenue Christchurch 8011 New ZealandChristchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group Department of Orthopaedic Surgery University of Otago Christchurch 2 Riccarton Avenue Christchurch 8011 New ZealandChristchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group Department of Orthopaedic Surgery University of Otago Christchurch 2 Riccarton Avenue Christchurch 8011 New ZealandChristchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group Department of Orthopaedic Surgery University of Otago Christchurch 2 Riccarton Avenue Christchurch 8011 New ZealandChristchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group Department of Orthopaedic Surgery University of Otago Christchurch 2 Riccarton Avenue Christchurch 8011 New ZealandChristchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group Department of Orthopaedic Surgery University of Otago Christchurch 2 Riccarton Avenue Christchurch 8011 New ZealandChristchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group Department of Orthopaedic Surgery University of Otago Christchurch 2 Riccarton Avenue Christchurch 8011 New ZealandChristchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group Department of Orthopaedic Surgery University of Otago Christchurch 2 Riccarton Avenue Christchurch 8011 New ZealandAbstract While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D‐bioassembly platform is introduced to primarily study fusion of cartilage–cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D‐bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type‐II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D‐model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high‐throughput 3D‐bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis.https://doi.org/10.1002/advs.2021033203D‐bioassemblycartilage tissuescocultured spheroidshigh throughputmicrotissuesspheroid fusion |
| spellingShingle | Gabriella C. J. Lindberg Xiaolin Cui Mitchell Durham Laura Veenendaal Benjamin S. Schon Gary J. Hooper Khoon S. Lim Tim B. F. Woodfield Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model Advanced Science 3D‐bioassembly cartilage tissues cocultured spheroids high throughput microtissues spheroid fusion |
| title | Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model |
| title_full | Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model |
| title_fullStr | Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model |
| title_full_unstemmed | Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model |
| title_short | Probing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model |
| title_sort | probing multicellular tissue fusion of cocultured spheroids a 3d bioassembly model |
| topic | 3D‐bioassembly cartilage tissues cocultured spheroids high throughput microtissues spheroid fusion |
| url | https://doi.org/10.1002/advs.202103320 |
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