There is a need of tools to evaluate and predict the safety and success of cell-based treatments in earlier stages. The current lack of methods providing real-time tracking of transplanted cells and knowledge on their early biodistribution and viability is one of the major weakness of the available cell-based treatments. These treatments can sometime be ineffective due to poor or unspecific targeting or lead to tumor developments. Therefore, to fulfill this need, nTRACK develops a safe and highly sensitive multimodal nanoimaging agent enabling non-invasive and quantitative stem cell tracking in the entire body.
The principle of nTRACK is to insert iron oxide nanoparticles with a gold shell in stem cells and inject those labelled stem cells in the body in order to foster muscle regeneration. The nanoparticles allow a precise tracking of the stem cells up to the injured organ of the body. This bimodal technology tracks cells with Computer Tomography (CT) thanks to the gold shell and with Magnetic Resonance Imaging (MRI) sensitive to the presence of iron.
The project focuses on four main domains of activities. First, the production of the nanoparticles by using manufacturing methods that complies Good Manufacturing Practices (GMP), mainly by a German company, MJR PharmJet. The particles are inserted in the stem cells provided by Pluristem, an Israeli company. Two strategies have been developed due to differences in development velocities. One where the nanoparticles are only made of gold fulfilling the GMP standard but not compatible with MRI. The second one consists of the iron oxide nanoparticle with gold shell by the Bar-Ilan University (Israel), but their manufacturing method does not fulfill the GMP requirements, yet.
Second, the proof of concept aims to show that the contrasting agent is working correctly with the different imaging techniques such as CT and MRI. Depending on the strategy, stem cells with different types of nanoparticles are being used during in-vivo studies. BIOEMTECH, a Greek company develops an AI algorithm capable of counting the stem cells in the targeted body part and identify migration patterns.
Third, LEITAT is conducting jointly with Vivotecnia in vitro immunotoxicity and genotoxicity studies and exploratory toxicokinetic assays in rodents to support the design of the main preclinical safety regulatory studies. The studies in rats will allow selecting the most relevant administration method and animal model and adequate follow-up periods. From the data analyzed up to now, no relevant toxic effects have been observed after a single intravenous or intramuscular administration of nTRACK nanoparticles in SD rats up to a follow-up period of 8 weeks. The VHIR is carrying out the generation and the revision of all the medical image studies and they have designed its model with muscle regeneration prediction algorithms based on machine learning. Furthermore, they have recently submitted a publication where they have been able to predict the muscle regeneration of a small animal with an unusual radiological technique, such as TAC, which is a huge achievement.
Lastly, the regulatory part prepares the market entry of the technology in direct contact with regulatory authorities. Discussions with the European Medical Agency (EMA) Innovation Task Force resulted in recommendations on the categorization of the nTRACK technology. Further work by Asphalion, a Spanish Consultancy on Scientific and Regulatory Affairs and RIVM, the Dutch National Institute for Public Health and the Environment, is currently being carried out with National Competent Authorities to seek scientific advice on the studies planned.
The first n-TRACK Open Day Workshop was organised by Cambridge Nanomaterials Technology Ltd at Trinity Hall College in Cambridge, UK on 30th October 2019 with the aim to link the partners with new collaborators and to support further exploitation of the project results. The workshop took place at the Lecture Theatre with a small exhibition held at the back of the room where posters and exhibition stands from the project partners’ were displayed. Partners were given the opportunity to present themselves and non-confidential project results in front guest participating organisations such as Novo Nordisk, STEMCELL Technologies, Johnson Matthey, Wellcome – MRC Cambridge Stem Cell Institute – University of Cambridge, Cell and Gene Therapy Catapult, Great Ormond Street Hospital – UCL Institute of Child Health – Stem Cells and Regenerative Medicine Section and Dolomite Microfluidics, among others.