TR&D 4

Overview: Extracellular vesicles as a nanotheranostic platform in neuroinflammation​

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Mesenchymal stem or stromal cells (MSCs) are non-hematopoietic multipotent stem cells initially isolated from bone marrow, but known to be present in many other tissues. They are currently one of the most widely used stem cells for treatment of a plethora of diseases including ischemic heart disease, osteoarthritis, diabetes mellitus, neurological disorders, and cancer, with over 1,300 registered clinical trials. They secrete beneficial factors that have anti-apoptotic, proangiogenic, neuroprotective, and immunomodulatory properties, and lack some of the ethical and tumorigenic safety concerns associated with pluripotent stem cells. MSCs have also been termed “medicinal signaling cells”, as they secrete multiple beneficial factors in the form of extracellular vesicles (EVs) that have trophic homing properties
to sites of inflammation, in particular neuroinflammation such as encountered in stroke, multiple sclerosis (MS), and amytrophic lateral sclerosis (ALS). However, the use of MSCs is limited by complex regulatory issues and logistics, low cell viability, and high costs. The field of cell therapy has now been shifting to the production of EVs as a “cell-free” alternative. Similar to tracking whole cells, it will be imperative to be able to track the biodistribution of these therapeutic EVs in vivo in order to interpret and improve therapeutic outcome. The overarching goal of this TR&D is to develop methods to track MSC-EVs in vivo and to disseminate these (labeled) products to the scientific community.

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Aim 1: To develop magnetically labeled MSC-EVs as a bimodal (negative) MRI contrast agent and superparamagnetic iron oxide (SPIO) magnetic particle imaging (MPI) tracer.

Aim 2: To develop gadolinium-labeled MSC-EVs as positive MRI contrast agent.

Aim 3: To develop unlabeled MSC-EVs as a diaCEST MRI contrast agent.

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Aim 4: To validate the trophic properties of labeled and unlabeled EVs for (neuro)inflammation in vivo using a mouse model of MS.