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Details of Grant 

EPSRC Reference: EP/L006472/1
Title: Generation of Multi-Modal Imaging Mesenchymal Stem Cells
Principal Investigator: Kalber, Dr T
Other Investigators:
Lythgoe, Dr M
Researcher Co-Investigators:
Project Partners:
Department: Medicine
Organisation: UCL
Scheme: EPSRC Fellowship
Starts: 01 April 2014 Ends: 31 March 2019 Value (£): 933,494
EPSRC Research Topic Classifications:
Med.Instrument.Device& Equip. Tissue Engineering
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
15 Jan 2014 Eng Fellowship Interviews Jan 2014 Announced
01 Oct 2013 Engineering Prioritisation Meeting 1 October 2013 Announced
Summary on Grant Application Form
Context of the Research

Regenerative Medicine has the potential to transform medicine and provide treatments and cures in areas of unmet need. Cell therapies using mesenchymal stem cells (MSCs) are increasingly applied in clinical trials in areas such as stroke, heart disease and as adjuvant therapies for cancer. However, with all emerging technologies, there are a number of barriers to evaluating their potential effectiveness that need to be addressed, which is localised delivery to target tissue and functionality of the cells once in situ. The focus of my research programme will be to provide multi-modal cell labelling agents for complimentary imaging technologies that can be utilized together to provide a clear understanding of the mechanisms of delivery and uptake with functional cell survival so that scientific beneficiaries (academics, clinicians, pharmaceutical companies, biotechnology companies, regulatory authorities) are able to accelerate these new medicines to other areas of regenerative medicine as well as translation to the human population with full confidence.

The monitoring the delivery and tracking the viability of cells once transplanted into patients is of particular importance not only for the assessment of both the degree and duration of therapeutic efficacy but also for patient safety. Identification of the optimal route of administration, the degree and longevity of cell uptake and routes of clearance can identify possible organs of risk while potentially limiting the number of repeat injections or surgeries required per patient.

Iron oxide nanoparticle have shown promise in localizing stem cells to defined areas of disease by magnetic resonance imaging, MRI) and a number of these nanoparticles have been previously been approved for clinical use. However, they do not currently display the necessary characteristics for the sensitivity that is required to track transplanted cells or provide information on their functionality in vivo. However, other imaging modalities such as nuclear medicine (SPECT/CT) are capable of tracking cells throughout the body, albeit with poor resolution and with new developments in molecular biology are capable of assessing cell viability in vivo. However, at present one imaging modality and one imaging probe cannot provide the information required for the complete characterization of cell therapeutics.

The new technologies we propose therefore combines innovative molecular biology approaches with nanochemistry to generate multi-modal imaging MSC for in vivo imaging with complimentary preclinical imaging modalities (MRI, SPECT/CT, photoacoustic and bioluminescent imaging). We aim to label cells with both reporter genes and nanopartlces, uniting imaging platforms and imaging probes to utilize the most favourable components of each while reducing their limitations. We will then utilize this to quantify delivery and monitor the localisation and viability of transplanted cells to clinically relevant models of tumours. We will identify the optimal routes of administration and the longevity of cell survival and apply this knowledge to optimize the subsequent application and dosing regimens of our therapeutic MSCs as anti-cancer delivery vehicles. Although this proposal is based on stem cells as adjuvant therapies for cancer the use of our labelling technologies for cell trafficking can be applied to other stem cells and regenerative medicines. Merge this with clinically translatable MR imaging endpoints to provide a full assessment of the efficacy of the cell therapy will therefore accelerate these therapies into mainstream clinical practise.

Key Findings
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Potential use in non-academic contexts
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Date Materialised
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