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Cartilage tissue engineering using human embryonic stem cells

Cartilage tissue engineering using human embryonic stem cells
Cartilage tissue engineering using human embryonic stem cells
Osteoarthritis (OA) is the most prevalent joint disease and is a leading cause of disability, particularly amongst the elderly. OA is caused by articular cartilage degradation. Hyaline articular cartilage covers the ends of bones and enables the smooth articulation of joints by reducing friction and functioning as a shock absorber. Articular cartilage is susceptible to damage and due to its avascular phenotype, self-repair is limited. Current early intervention strategies, including autologous chondrocyte implantation, typically produce fibrous rather than hyaline cartilage and frequently fail to provide a long-term solution. Most patients ultimately require total joint replacement surgery, a late stage treatment option that carries appreciable risks. An alternative early intervention treatment that focusses on replacing damaged tissue with hyaline cartilage is required; tissue engineering provides a platform to move from cell- to tissue-based treatments and facilitates the in vitro generation of hyaline tissue for cartilage repair. Human embryonic stem cells (hESCs) are pluripotent and therefore have the potential todifferentiate into cells from all three germ layers. They can also proliferate indefinitely in vitro without showing signs of cellular senescence. hESCs therefore overcome many of the limitations associated with primary chondrocytes and adult stem cells.This study demonstrates the generation of a successful and highly reproducible protocol for the generation of hESC-derived cartilage. hESC-derived chondrocytes formed mechanically-stable hyaline-like cartilage in pellet culture that was able to repair a partial-thickness defect in ex-vivo organotypic culture. Furthermore, co-culture of hESC-derived cartilage pellets with native cartilage enabled the generation of previously unattainable volumes of healthy hyaline-like cartilage, exceeding 6mm in diameter. In conclusion, this thesis demonstrates the scaffold-free generation of healthy, hyaline tissue engineered cartilage on a scale that has not previously been demonstrated. Use of hESC-derived chondrocytes has overcome limitations of scale-up and has enabled the development of bioengineered cartilage of clinically relevant proportions. This work provides compelling evidence for the use of hESC-derived cartilage in the development of new treatments for cartilage damage.
University of Southampton
Griffith, Lauren Asha
effb7a8b-c625-4c21-b390-ad3ab2677705
Griffith, Lauren Asha
effb7a8b-c625-4c21-b390-ad3ab2677705
Houghton, Franchesca
53946041-127e-45a8-9edb-bf4b3c23005f
Tare, Rahul
587c9db4-e409-4e7c-a02a-677547ab724a

Griffith, Lauren Asha (2020) Cartilage tissue engineering using human embryonic stem cells. Doctoral Thesis, 329pp.

Record type: Thesis (Doctoral)

Abstract

Osteoarthritis (OA) is the most prevalent joint disease and is a leading cause of disability, particularly amongst the elderly. OA is caused by articular cartilage degradation. Hyaline articular cartilage covers the ends of bones and enables the smooth articulation of joints by reducing friction and functioning as a shock absorber. Articular cartilage is susceptible to damage and due to its avascular phenotype, self-repair is limited. Current early intervention strategies, including autologous chondrocyte implantation, typically produce fibrous rather than hyaline cartilage and frequently fail to provide a long-term solution. Most patients ultimately require total joint replacement surgery, a late stage treatment option that carries appreciable risks. An alternative early intervention treatment that focusses on replacing damaged tissue with hyaline cartilage is required; tissue engineering provides a platform to move from cell- to tissue-based treatments and facilitates the in vitro generation of hyaline tissue for cartilage repair. Human embryonic stem cells (hESCs) are pluripotent and therefore have the potential todifferentiate into cells from all three germ layers. They can also proliferate indefinitely in vitro without showing signs of cellular senescence. hESCs therefore overcome many of the limitations associated with primary chondrocytes and adult stem cells.This study demonstrates the generation of a successful and highly reproducible protocol for the generation of hESC-derived cartilage. hESC-derived chondrocytes formed mechanically-stable hyaline-like cartilage in pellet culture that was able to repair a partial-thickness defect in ex-vivo organotypic culture. Furthermore, co-culture of hESC-derived cartilage pellets with native cartilage enabled the generation of previously unattainable volumes of healthy hyaline-like cartilage, exceeding 6mm in diameter. In conclusion, this thesis demonstrates the scaffold-free generation of healthy, hyaline tissue engineered cartilage on a scale that has not previously been demonstrated. Use of hESC-derived chondrocytes has overcome limitations of scale-up and has enabled the development of bioengineered cartilage of clinically relevant proportions. This work provides compelling evidence for the use of hESC-derived cartilage in the development of new treatments for cartilage damage.

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Cartilage Tissue Engineering Using Human Embryonic Stem Cells - Version of Record
Restricted to Repository staff only until 31 March 2023.
Available under License University of Southampton Thesis Licence.
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Permission to deposit thesis form 201920
Restricted to Repository staff only
Available under License University of Southampton Thesis Licence.
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Declaration of Authorship
Restricted to Repository staff only
Available under License University of Southampton Thesis Licence.

More information

Published date: March 2020

Identifiers

Local EPrints ID: 449349
URI: http://eprints.soton.ac.uk/id/eprint/449349
PURE UUID: 64d4fb85-1bc3-4e20-80fd-f4acef26b42d
ORCID for Franchesca Houghton: ORCID iD orcid.org/0000-0002-5167-1694
ORCID for Rahul Tare: ORCID iD orcid.org/0000-0001-8274-8837

Catalogue record

Date deposited: 25 May 2021 16:35
Last modified: 13 Dec 2021 02:56

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Contributors

Author: Lauren Asha Griffith
Thesis advisor: Franchesca Houghton ORCID iD
Thesis advisor: Rahul Tare ORCID iD

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