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Details of Grant 

EPSRC Reference: EP/X018776/1
Title: GlycoMatrix: Engineering Tunable Stem Cell Niches Enhanced with Glycosaminoglycan Instructive Cues
Principal Investigator: Turnbull, Professor J
Other Investigators:
Guimond, Dr S Kehoe, Dr O Chari, Professor DM
Researcher Co-Investigators:
Project Partners:
IntelliHep Ltd SpheriTech Ltd University of North Carolina Chapel Hill
Victoria University of Wellington
Department: Faculty of Natural Sciences
Organisation: Keele University
Scheme: Standard Research - NR1
Starts: 01 January 2023 Ends: 30 November 2024 Value (£): 202,139
EPSRC Research Topic Classifications:
Biomaterials Tissue engineering
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
21 Jun 2022 New Horizons 2021 Full Proposal Panel Announced
23 Jun 2022 New Horizons Biomedical and Chemical Engineering Panel June 2022 Announced
Summary on Grant Application Form

The use of stem cells for novel disease treatments is in its infancy and shows great promise, holding huge potential to revolutionize medicine. However, a major challenge for exploiting the full potential of stem cells are the limitations imposed by (1) lack of defined, non-animal-derived materials for growing stem cells, (2) control of their development into specific cell types for treatments (eg. neurons or bone cells), and (3) production of clinically compatible and effective scaffolds with favourable properties for transplanting for repair or disease treatments.

In nature specific cell types develop from stem cells in a local environment (a matrix of many molecules) called a "niche", but the full range of controlling cues in these niches are poorly understood. The chemical and physical properties of growth surfaces, along with added proteins, have been explored, but not the role of specialised sugars (glycans) called glycosaminoglycans (GAGs), especially a class called heparan sulfates (HS), which are related to the blood-thinning drug heparin. These are a structurally diverse class of sulphated sugars found in the stem cell niche that are master regulators of stem cells via regulating many protein factors that control cell growth and development. The key challenge we will address is to show that unique HS structures - "cues" - can be exploited to create tunable fully-defined and clinically-compatible matrix materials as substrates to control cell growth and fate decisions by stem cells.

HS have been under-exploited due to technical barriers to study of their structure-function, but can now be tackled for the first time by integrating recent advances in synthesis, analytical methods and stem cell screening. We will produce a unique library of HS compounds and screen their activity in test-bed stem cell applications, namely the enhanced production of bone-forming chondrocytes, and neuronal cells for nerve repair. We hope to establish a strategy for creating multimodal, 'pro-healing' medical biomaterials for orthopaedic and neurological repair. With success this project would open up major new opportunities for generation and control of specific stem cell types & establishment of protocols compatible with clinical grade manufacturing of biomaterials for diverse regenerative medicine applications.

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Organisation Website: http://www.keele.ac.uk