3D Nanodiamond structures as a platform for the spontaneous differentiation of neural and adipose stem cells
Lead Research Organisation:
University College London
Department Name: Structural Molecular Biology
Abstract
Strategic Research Priority: World Class Bioscience
Abstract
The bio-activity of functionalised nanodiamonds has shown to induce the spontaneous neural stem cell (NSC) differentiation into neurons. This incorporated with the development of a 3D nanodiamond scaffold enables the investigation of 3D neural network formation from stem cells. Moreover, the antioxidant effect of the nanodiamonds offers exciting opportunities for the therapeutic treatment of neural injury/stroke. This project uniquely combines cutting edge analysis of human NSC and neuron response to neurotoxic damage and possible protective effect of nanodiamods with the engineering of bio-active 3D nanodiamond scaffolds.
Project
Stem cells (SCs) represent an exciting opportunity to generate tissues in vitro for transplant therapies or drug screening. It is important to precisely control the differentiation of such tissues. Nanodiamonds have been shown to promote the adhesion and proliferation of neurons and neural SCs. (1, 2) This remarkable property for an otherwise bioinert material is not observed on diamond, (3) but only on nanodiamonds (~5nm), whose variable surface functional groups can encourage protein absorption. It is also likely that the topology of nanodiamonds is favorable for cell attachment. (4) Moreover, controlling the surface properties of the nanodiamonds can lead to differing outcomes in terms of SC fate and confluency. Unusually nanodiamonds are able to promote spontaneous differentiation of neural SCs into neurons without the need for inducing growth factors. Studies have concentrated on planar surfaces; a more typical cell environment is desirable for the generation of fully interconnected neural networks, which would be 3D. The proposed PhD aims to extend previous work with nanodiamonds into 3D SC derived functional neural networks. A novel process to produce 3D structured surfaces displaying bio-versatile properties of nanodiamonds will be pursued. This will involve the fabrication of 3D scaffolds from bioinert graphene materials (5) but in this novel case coated with functionlised nanodiamonds to impart the desired bioactivity for SCs. This exciting PhD will combine state of the art SC biology with the development of optimally engineered bio-active 3D nanodiamond structures. In particular, the student will undertake engineering research to generate 3D graphene scaffolds and the attachment of chemically functionalised nanodiamonds that will support NSC growth and differentiation. In terms of cell biology, human NSC and neurones carrying fluorescent death-associated protein sensors will be generated to assess their response to neurotoxic damage in the novel 3D nanodiamond scaffolds and their protective effect
Abstract
The bio-activity of functionalised nanodiamonds has shown to induce the spontaneous neural stem cell (NSC) differentiation into neurons. This incorporated with the development of a 3D nanodiamond scaffold enables the investigation of 3D neural network formation from stem cells. Moreover, the antioxidant effect of the nanodiamonds offers exciting opportunities for the therapeutic treatment of neural injury/stroke. This project uniquely combines cutting edge analysis of human NSC and neuron response to neurotoxic damage and possible protective effect of nanodiamods with the engineering of bio-active 3D nanodiamond scaffolds.
Project
Stem cells (SCs) represent an exciting opportunity to generate tissues in vitro for transplant therapies or drug screening. It is important to precisely control the differentiation of such tissues. Nanodiamonds have been shown to promote the adhesion and proliferation of neurons and neural SCs. (1, 2) This remarkable property for an otherwise bioinert material is not observed on diamond, (3) but only on nanodiamonds (~5nm), whose variable surface functional groups can encourage protein absorption. It is also likely that the topology of nanodiamonds is favorable for cell attachment. (4) Moreover, controlling the surface properties of the nanodiamonds can lead to differing outcomes in terms of SC fate and confluency. Unusually nanodiamonds are able to promote spontaneous differentiation of neural SCs into neurons without the need for inducing growth factors. Studies have concentrated on planar surfaces; a more typical cell environment is desirable for the generation of fully interconnected neural networks, which would be 3D. The proposed PhD aims to extend previous work with nanodiamonds into 3D SC derived functional neural networks. A novel process to produce 3D structured surfaces displaying bio-versatile properties of nanodiamonds will be pursued. This will involve the fabrication of 3D scaffolds from bioinert graphene materials (5) but in this novel case coated with functionlised nanodiamonds to impart the desired bioactivity for SCs. This exciting PhD will combine state of the art SC biology with the development of optimally engineered bio-active 3D nanodiamond structures. In particular, the student will undertake engineering research to generate 3D graphene scaffolds and the attachment of chemically functionalised nanodiamonds that will support NSC growth and differentiation. In terms of cell biology, human NSC and neurones carrying fluorescent death-associated protein sensors will be generated to assess their response to neurotoxic damage in the novel 3D nanodiamond scaffolds and their protective effect
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M009513/1 | 01/10/2015 | 31/03/2024 | |||
| 1627271 | Studentship | BB/M009513/1 | 01/10/2015 | 30/09/2019 | Despoina Paschou |
| Description | I have discovered that adipose-derived stem cells, which are stem cells that we get from the fat tissue, show affinity to nanodiamonds, especially nanodiamonds that have been functionalised with either hydrogen or oxygen. This affinity is interpreted as better viability after a week of proliferation on borosilicate glass coverslips seeded with nanodiamonds and as better percentages of differentiation into cartilage. In 2019, I discovered that adipose-derived stem cells show affinity to oxygen-terminated nanodiamonds. I also discovered that the morphology of the substrate on which the ADSCs are grown on, affects their proliferation and differentiation potential. I also discovered that putting nanodiamonds in polymer scaffolds increases their mechanical properties in a significant way and we can use them in order to achieve scaffolds with similar mechanical properties to those of in vivo tissue. |
| Exploitation Route | My findings can be used by individuals in order to understand better the environments in which adipose-derived stem cells thrive. We can also use them to see whether the use of nanodiamonds in hADSC differentiation can have an impact on the spontaneous differentiation of hADSCs in different tissue types. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology,Other |
| Description | NIHR Great Ormond Street Hospital Biomedical Research Centre Family Fun Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | During the open day, we organised 'stations' with interactive activities that introduce young people to the research of our laboratory. We demonstrated through play and displays the work that our laboratory does in a meaningful and engaging way. We engaged with more than 200 kids and their parents during the day. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Organising comittee of the DBC symposium |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | 80 researchers from the Developmental Biology Unit of the UCL Institute of Child Health attended the 6th and 7th DBC symposia, which was organised by early-stage researchers from the unit, including myself. In both symposia, an external keynote speaker was invited, which covered a topic of broad interest in developmental biology. The rest of the symposium consisted of 5- and 20-minute long presentations by early-stage researchers in the unit. The best talks were judged by a committee of post-doctoral fellows and were awarded. The impact of the symposia was better understanding and collaboration facilitation among the different departments of the developmental biology unit, and increased attendance was observed between the two symposia I helped organise. |
| Year(s) Of Engagement Activity | 2017 |
| Description | PhD Tutor at the Brilliant Club |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The Brilliant Club is an educational charity that connects PhD researchers with under-represented schools in the UK. These schools have a student body that for the most part does not continue in selective higher educational institutions, despite their good grades at GCSE level. My job as a PhD research was to design and deliver 6 tutorials on the subject of my research. I created a 100-page workbook with information on my area of research, gave the students assignments that encouraged the development of their critical and science communication skills and allocated a final assignment where they had to create a 2000 research proposal based on the discussions we had in class and the materials provided. These students came from 2 different schools in London and are in Years 9 and 10. |
| Year(s) Of Engagement Activity | 2018 |