The Gentleman lab works at the interface of stem cell biology, chemistry and materials science to develop innovative biomaterials for regenerative medicine. We aim to understand how materials and their properties from the nano- to macro-scales affect stem cells. We then exploit these insights to develop 3D materials that can effectively direct stem cell differentiation for tissue engineering.

Projects

Intestinal organoids to explore ECM remodelling in inflammatory bowel disease (IBD)
IBD is marked by the formation of fistulae or fibrosis, in which the extracellular matrix (ECM) either degrades or is stiffened; but it remains unclear if ECM changes are a consequence of inflammation or if they contribute to disease pathology. This project aims to create an IBD model ‘in-a-dish’ by combining synthetic hydrogels that allow for ECM remodelling with intestinal organoids differentiated from human induced pluripotent stem cells. Using proteomic and microrheological techniques, we explore how modulating peri-organoid ECM composition affects epithelial susceptibility to inflammation, providing mechanistic insights into IBD pathology and potentially facilitating the development of novel therapeutic strategies.

Engineering the articular surface of the temporomandibular joint (TMJ)
The articular surface of TMJ has a poor healing capacity, leaving few options for patients with painful degenerative diseases. In this project, we develop a hydrogel-based materials that can promote regeneration of focal defects of the TMJ articular surface. Our material is based on an injectable hydrogel scaffold that can encapsulate autologous cells, bind to the surrounding native tissue and drive region-specific osteo- and fibrochondrogenesis.

Harnessing secreted matrix proteins to regulate stem cell differentiation in 3D
We have recently shown that mesenchymal stem cells encapsulated within hydrogels quickly modify their local surroundings by secreting and assembling proteins pericellularly. This secreted matrix quickly alters the biochemical composition and local mechanical environment around cells, modulating cellular mechanotransduction and fate specification (Ferreira et al. Nat Commun 2018). In this project, we use a combination of transcriptomics and proteomics to identify specific secreted proteins that direct cell response in 3D materials. We then design hydrogel-based materials that can capture specific secreted proteins so that we can exploit this effect to create functional engineered tissues.
Publications
Awards
- Koch Institute Image Award 2016 from the Koch Institute for Integrative Cancer Research at MIT
- Wellcome Image Award 2016 for ‘Human stem cell embedded in a 3D matrix’
- Philip Leverhulme Prize in Engineering for outstanding work in Regenerative Medicine (2013)
- Wellcome Trust Research Career Development Fellowship 2011-2017 “Engineering functional bone-soft tissue interfaces: Novel approaches to musculoskeletal regenerative medicine”
News
Royal Society Pairing Scheme – A Week in Westminster
Earlier this year, Dr Eileen Gentleman, Academic Lead for Impact, participated in the Royal Society Pairing Scheme Week in Westminster. In this short blog,...

Projects

Intestinal organoids to explore ECM remodelling in inflammatory bowel disease (IBD)
IBD is marked by the formation of fistulae or fibrosis, in which the extracellular matrix (ECM) either degrades or is stiffened; but it remains unclear if ECM changes are a consequence of inflammation or if they contribute to disease pathology. This project aims to create an IBD model ‘in-a-dish’ by combining synthetic hydrogels that allow for ECM remodelling with intestinal organoids differentiated from human induced pluripotent stem cells. Using proteomic and microrheological techniques, we explore how modulating peri-organoid ECM composition affects epithelial susceptibility to inflammation, providing mechanistic insights into IBD pathology and potentially facilitating the development of novel therapeutic strategies.

Engineering the articular surface of the temporomandibular joint (TMJ)
The articular surface of TMJ has a poor healing capacity, leaving few options for patients with painful degenerative diseases. In this project, we develop a hydrogel-based materials that can promote regeneration of focal defects of the TMJ articular surface. Our material is based on an injectable hydrogel scaffold that can encapsulate autologous cells, bind to the surrounding native tissue and drive region-specific osteo- and fibrochondrogenesis.

Harnessing secreted matrix proteins to regulate stem cell differentiation in 3D
We have recently shown that mesenchymal stem cells encapsulated within hydrogels quickly modify their local surroundings by secreting and assembling proteins pericellularly. This secreted matrix quickly alters the biochemical composition and local mechanical environment around cells, modulating cellular mechanotransduction and fate specification (Ferreira et al. Nat Commun 2018). In this project, we use a combination of transcriptomics and proteomics to identify specific secreted proteins that direct cell response in 3D materials. We then design hydrogel-based materials that can capture specific secreted proteins so that we can exploit this effect to create functional engineered tissues.
Publications
Awards
- Koch Institute Image Award 2016 from the Koch Institute for Integrative Cancer Research at MIT
- Wellcome Image Award 2016 for ‘Human stem cell embedded in a 3D matrix’
- Philip Leverhulme Prize in Engineering for outstanding work in Regenerative Medicine (2013)
- Wellcome Trust Research Career Development Fellowship 2011-2017 “Engineering functional bone-soft tissue interfaces: Novel approaches to musculoskeletal regenerative medicine”
News
Royal Society Pairing Scheme – A Week in Westminster
Earlier this year, Dr Eileen Gentleman, Academic Lead for Impact, participated in the Royal Society Pairing Scheme Week in Westminster. In this short blog,...

Group lead
Contact us
Dr Eileen Gentleman
Reader in Bioengineering and Principal Investigator
Guy's Tower Wing
Guy's Hospital