Magnetic Targeting of Stem Cells

Stem cell therapy is one of the most exciting and promising areas for disease treatment and reparative medicine. Stem cells are produced by the body as a 'universal' type of cell that is capable of replacing many tissues when they are damaged or worn out. One of the major problems with using stem cells therapeutically are that stem cells do not automatically home to the area of damage. From previous studies we know that after injury only limited numbers of injected stem cells will go to the site of damage. In this study we will develop new magnetic technique that will allow us to guide stem cells to the site of injury, which we hope will improve the therapeutic benefit of the stem cells. To do this we will tag stem cells with magnetic nanoparticles and steer them to sites of tissue damage in the body, using external magnetic fields. Superparamagnetic nanoparticles offer attractive possibilities in medicine. Firstly, they have controllable sizes ranging from a few nanometres up to tens of nanometres, which places them at dimensions that are smaller than or comparable to those of a cell (10-100 um), a virus (20-450 nm), a protein (5-50 nm) or a gene (2 nm wide and 10-100 nm long). This means that they can be incorporated into a cell, thereby providing a controllable means of 'tagging'. Secondly, the nanoparticles are magnetic, which means that they can be mechanically manipulated by an external magnetic field gradient. In our study, we want to use this property to enable site-specific localisation of magnetically tagged stem cells by the use of an externally applied magnetic field. Thirdly, superparamagnetic iron oxide particles 'show up' on magnetic resonances images, thus offering an approach to tracking these particles. For this project, we will develop a novel technology for guiding stem cells. Magnetic resonance imaging (MRI) systems have traditionally been used for imaging. Here we will modify their use to guide as well as track stem cells. In this study we aim to magnetically tag stem cells with superparamagnetic nanoparticles. Using cell cultures we will assess the effects of magnetic fields on cell viability and cell differentiation. Subsequently, we will investigate the uptake of labelled cells in animal models of vascular damage, and assess whether the stem cells have integrated into the damaged tissue. We will monitor whether the stem cells have attached to the areas of damage using MRI, as the magnetic iron-oxide particles appear as dark areas on the image. We will also use an iron detector know as a SQUID to measure exactly how many iron particles have attached to the cells. Varying both nanoparticles and magnetic field strength in vivo will enable assessment of the effects of flow rates and field strength on localisation of the labelled cells. We believe that if this novel technology is successful we will be able to guide delivery of stem cells to other regions of the body, such as the brain or liver, for the restoration of function in damaged or diseased tissue, which may open a new area of investigation for site-specific delivery of stem cells or genetically altered cells.

The work proposed here has the potential to move stem cell therapies closer to more widespread clinical application. The technology has widespread application in stem cell therapy and addresses several of the current barriers to clinical translation in chronic wounds or disease. The ability to accurately target and retain the stem cells at the site of injury or disease where inflammatory cues may not be present. By solving this problem using the novel properties of magnetic nanoparticles and their responses to applied fields, we plan to provide the important tools needed to realize the full potential of stem cell therapy Benefit to the patient: Stem cells have the potential to treat a myriad of conditions that affect our wellbeing including diseases such as cancer and genetic disorders which affect an entire population, as well as diseases and tissue degeneration associated with an aging population, such as neurodegenerative diseases, heart and respiratory ailments and osteoarthritis. In addition, these cells hold great promise in the treatment and regeneration of tissue damaged in traumatic injury. Though the work proposed here is aimed at cardiovascular disease, the technology that we propose to develop will apply to a vast array of diseases and traumas. Any indication for which specific targeting of stem cells is required will be applicable. Benefit to Industry: Our commercial partners bring product development expertise to the current phase, as well as the skills required to take magnetic targeting into hospitals and clinics in the future. Existing collaborations include Chemicell and Micromod, magnetic particle manufacturers, which specialise in biofunctionalisation for diagnostics. Bayer-Schering Pharma is a major pharma corporation and the manufacturer of Resovist, whose contrast media division sees MRT as opening up new product streams. Varian Inc is an international medical imaging/devices company and a potential manufacturing and/or distribution partner. Awareness of the public: Our public partners are the patient advocacy and support groups with whom we already have strong links, and from whom we regularly seek feedback and comment. These include British Heart Foundation, Cancer Research UK, The British Lung Foundation, and engaged end-user groups within our hospitals. Industry-academic partnerships in stem cell work will increase in the coming years, and public understanding and support will be needed to maximise chances of success. Therefore, we will prioritise approaches to improve the public perception of the value of novel technologies such as magnetic nanoparticles in stem cell discovery and development. Collaboration and Capability: The Clinical Advisory Board (see case for support) together with the applicants are already well placed to maximise impact of this research in many spheres. To build on our existing collaboration and interactions with industry, end-users of our technologies and the patient community, we will appoint the new PDRA to the role of 'Impact' Coordinator. This will provide a contact who is responsible for ensuring a coordinated plan between members of the two group for maximising impact from our EPSRC funded research. In addition, the forum led by the coordinator will provide an excellent training opportunity for the staff appointed to the project in the importance and understanding of how we ensure 'impact' of our newly developed technologies.