BioMASCE · Biophysical Manipulation of Adult Stem Cell Epigenetics (BioMASCE) By Cell-Penetrating Nanoneedle Substrates
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-06-01 → 2018-05-31
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Biophysical Manipulation of Adult Stem Cell Epigenetics (BioMASCE) By Cell-Penetrating Nanoneedle Substrates
Signals from the extracellular environment are highly influential on cell behaviour. In particular, physicochemical cues from the materials upon which cells are cultured can drive fundamental changes to cell identity. Over the past two decades, a number of studies have demonstrated that complex interactions between cells and engineered materials can be manipulated in order to generate desired outcomes in cell fate and function, but these have consistently targeted the cell membrane and therefore have indirect consequences on intracellular machinery. In contrast, materials that exhibit the ability to simultaneously influence the classical machinery located at the cell membrane while also modulating the functions of intracellular processes, such as gene transcription or organization of intranuclear cargo, would provide new bioengineering methods for controlled regulation of cell function. In this project, porous silicon nanoneedle (nN) arrays were interfaced with human mesenchymal stem cells (hMSCs) in order to directly affect multiple components of the cell. Our findings indicate that nN interfacing leads to a range of biophysical changes within the cell, including accumulation of structural components of the nuclear envelope, functional decoupling of mechano-sensitive transcriptional regulators, and disruption of a steady-state epigenetic program within the cells. This work has showcased the ability of nano-structured materials to regulate high-level biological functions in human stem cells, and offers unique insight for applying next-generation materials for directing cell behaviours in the context of tissue engineering, regenerative medicine, and stem cell biology.
Data: CORDIS, © European Union
Project objective
Human mesenchymal stem cells (hMSCs) are a promising cell source for regenerative therapies. In part, their capacity for multi-lineage differentiation and subsequent therapeutic efficacy is controlled by the epigenetic status of the DNA. The Stevens Group at Imperial College London (ICL) has recently developed a novel material platform of porous silicon (pSi) nanoneedles (nNs) that penetrate the cell membrane, stimulating physical changes in the nucleus. Interestingly, nuclear mechanics and shape parameters have been shown to control epigenetic status in various cell types, but this remains under-investigated in hMSC. Therefore, in the present study, pSi nNs will be used to manipulate hMSC nuclear size and shape, as well as the resulting epigenetic status, as a means to identify novel mechanisms for enhancing differentiation capacity. The inherent porosity of the nNs, coupled with their ability for cell penetration, will be exploited as a delivery tool for a cutting-edge class of non-coding RNAs into hMSCs to interfere with, and further regulate, epigenetic status and resulting therapeutic potential. This discovery-driven project leverages a one-of-a-kind engineering tool for investigating and manipulating hMSC behaviour. In parallel, the applicant has proposed to undergo a secondment to a UK-based, non-academic partner organisation to enhance his knowledge of intellectual property protection, technology development, and product commercialisation in order to translate his research findings for clinical benefit. The applicant will increase his knowledge base during the project, creating new contacts in his personal network, as well as for the Stevens Group and ICL. This project represents a multidisciplinary, cutting-edge approach to stem cell biology and biomedical engineering, utilising cross-sectoral collaboration for enhanced training and potential for industrial translation of basic research findings.
Original text from CORDIS.
Participants
- IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union