Using a novel hydrogel and polymer surfaces to produce an in vivo like bone marrow niche for heamatopoietic stem cells in vitro.
Lead Research Organisation:
University of Glasgow
Department Name: College of Medical, Veterinary, Life Sci
Abstract
Studentship strategic priority area: Healthcare Technologies
Keywords: Hydrogels, polymers, materials characterisation, stem cells, stem cell niche
Absract: Haematopoietic stem cells (HSCs) are responsible for the production of the various cell types found in our blood. In vivo these cells are found in specialised microenvironments known as a stem cell niche within the bone marrow. In this stem cell niche HSCs are found alongside mesenchymal stem cells (MSCs) and other cells which help support and maintain the HSCs. The problem with current HSC research is the changing of cell phenotype, cell differentiation and loss of stemness when in vitro. This project looks to use novel hydrogels along with MSCs to reproduce the in vivo niche in vitro. Using poly(ethylene) glycol maleimide (PEGMAL) hydrogels as well as poly(ethyl) acrylate (PEA) surfaces. The stiffness of the gel can be altered by changing the ratio of PEGMAL to crosslinker added during gelation this is an important property of the gel as stiffness has been shown to have an influence in stem cell differentiation. Another addition to the gel is fibronectin (FN), a glycoprotein found in the extracellular matrix, which can aid in cellular adherence and allows the introduction of growth factors into the system. FN can also be adsorbed onto the PEA surface serving the same purpose as in the gel. Gel stiffness, crosslinking and composition as well as characterisation of the polymer surfaces will be considered using AFM, rheology, SEM, TEM and XPS. MSCs will be seeded into the bioengineered niches to look for niche marker expression (in cell western, PCR, flow cytometry) bure HSCs are added and characterised for self-renewal markers (flow cytometry).
Keywords: Hydrogels, polymers, materials characterisation, stem cells, stem cell niche
Absract: Haematopoietic stem cells (HSCs) are responsible for the production of the various cell types found in our blood. In vivo these cells are found in specialised microenvironments known as a stem cell niche within the bone marrow. In this stem cell niche HSCs are found alongside mesenchymal stem cells (MSCs) and other cells which help support and maintain the HSCs. The problem with current HSC research is the changing of cell phenotype, cell differentiation and loss of stemness when in vitro. This project looks to use novel hydrogels along with MSCs to reproduce the in vivo niche in vitro. Using poly(ethylene) glycol maleimide (PEGMAL) hydrogels as well as poly(ethyl) acrylate (PEA) surfaces. The stiffness of the gel can be altered by changing the ratio of PEGMAL to crosslinker added during gelation this is an important property of the gel as stiffness has been shown to have an influence in stem cell differentiation. Another addition to the gel is fibronectin (FN), a glycoprotein found in the extracellular matrix, which can aid in cellular adherence and allows the introduction of growth factors into the system. FN can also be adsorbed onto the PEA surface serving the same purpose as in the gel. Gel stiffness, crosslinking and composition as well as characterisation of the polymer surfaces will be considered using AFM, rheology, SEM, TEM and XPS. MSCs will be seeded into the bioengineered niches to look for niche marker expression (in cell western, PCR, flow cytometry) bure HSCs are added and characterised for self-renewal markers (flow cytometry).
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509668/1 | 01/10/2016 | 30/09/2021 | |||
| 1980274 | Studentship | EP/N509668/1 | 03/10/2016 | 30/06/2020 | Samantha Donnelly |
| Description | Retention of various growth factors within the hydrogel system that are required for HSC support and maintenance. The hydrogel properties have been shown to be unable to a suitable stiffness to represent the bone marrow niche. Microcarrier beads can be coated in PEA with FN adsorbed creating networks to which Growth factors can be tethered and cells attached. These can then be incorporated into the hydrogel system allowing MSCs to adhere and spread with the introduction of different growth factors to guide maintenance and differentiation of the population. |
| Exploitation Route | Other growth factors could be assessed in the system for maintaining other cell types in a 3D environment. The unable stiffness of the hydrogels means the system could be altered to represent other tissues to investigate other cell types e.g. stiffening the environment to mimic cancerous tissue. Using the PEA coated beads the growth factor can be altered to influence different cell outcomes e.g. angiogenesis, differentiation. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology,Other |
| Description | 2018 royal society summer exhibition London |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | The lab group as a whole was invited to the royal society summer exhibition in London where we were able to interact with a wide variety of people discussing our individual research s well as the labs research as a whole. The exhibit was visited by many schools and the general public as well as having a formal night time events with industry and other academics in attendance. This was a good opportunity to discuss my own research with the public and fellow researchers as well as a good networking opportunity. |
| Year(s) Of Engagement Activity | 2018 |
| Description | RSC Biomaterials meeting 2020 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Oral presentation on my research titled 'Using polyethylene glycol hydrogels to create an in vivo like bone marrow niche in vitro.' Focus was on the gel properties and the chemical characterisation of the PEA surfaces. The meeting was to show biomedical research with a chemistry connection with most participants coming from chemistry groups. The meeting allowed discussion with people in the field of biomedical research but from a different background. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Science Lates exhibition at the Glasgow Science Centre. |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | This is an evening event hosted at the Glasgow science centre aimed for adults to learn about science research, that is currently taking place, from different university groups around Scotland. Our aim was to engage with the general public and spark discussions on our research field. The audience showed an interest in the work and engage with the subject asking questions and starting discussions. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Scottish Science Advisory Council |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | This event involved communicating our research to members of the Scottish government and others in the scientific community. The event was intended to showcase top research that is currently taking place in Scotland and celebrate the world changing research that we have to offer. The audience had a strong interest in the impact of the research we were showing and how this could be developed further, many people showed an interest in our work and engaged in discussions. |
| Year(s) Of Engagement Activity | 2019 |
| Description | TERMIS 2019 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave an oral presentation on my project at the TERMIS EU charter conference 2019. The audience was international and engaged with my presentation with follow up questions. |
| Year(s) Of Engagement Activity | 2019 |