Project R-15260

Nanoghosts spooking away ischemic stroke (Research)

Ischemic stroke is a neurological disorder caused by a sudden disrupted blood supply of the brain. It is the second leading cause of death worldwide and often leads to permanent disabilities. Only a small proportion of patients can be adequately treated, highlighting the urgent need for new treatments. Mesenchymal stromal cells (MSC) and the membrane vesicles they produce, extracellular vesicles (EVs) have been proposed as an ideal therapy as they reduce the acute inflammation and also enhance blood vessel formation. However, their translation to the clinic is hampered by various problems. Recently, reconstructed cytoplasmic membranes of MSCs, designated as 'nanoghosts (NGs)' were shown to inherit the biological characteristics of the source cells and have prolonged shelf-life and high safety profile. The goal of my project is to develop NGs, derived from a superior MSC type, the dental pulp stem cells (DPSCs), as a treatment for ischemic stroke. I will not only study their angiogenic and immunomodulatory effects, but I will also enhance these properties by priming the parental cells, followed by an in-depth characterization of their lipid and protein content. Lastly, the therapeutic efficacy of the normal and primed NGs is investigated in two different rodent models of ischemic stroke. Insights obtained in this project will enhance our current knowledge of NGs as well as pave the way for potential clinical trials of this novel nanomedicine.

01 November 2024 - 31 October 2028