Engineering extracellular vesicles derived from human mesenchymal stem cells

Engineering extracellular vesicles derived from human mesenchymal stem
cells
Extracellular vesicles (EVs) are small, membranous, secreted carriers of proteins
and nucleic acids that enable cell-cell communication. They are evolutionarily
conserved (from yeast to human) and there is a growing interest in the use of
EVs in diverse biotechnological applications, particularly those secreted by
intrinsically regenerative cell types such as adult stem cells. We have
engineered several immortalised human clonal mesenchymal stem cell (MSC)
lines and demonstrated that they produce different types of EVs. In theory
therefore, these immortalised human cell lines may be used to produce an
inexhaustible supply of MSC-EVs. However, being able to control the efficiency
of EV generation, the EV cargo and target cell type would have distinct
biotechnological advantages. This project will build on the mechanistic
knowledge in yeast genetics and EV biology to develop bioengineered MSC-EV
production platforms.
Specific objectives are to:
-Characterise native MSC-EVs and optimise their isolation.
-Determine the underlying mechanisms to help direct and/or enrich cargo-
loading in MSC-EVs
-Engineer MSC-EVs to target specific cell types.
The project will be co-supervised by Professor Paul Genever and Dr. Chris
MacDonald who have broad expertise in MSC biology, EV production, stem cell
and yeast model systems, endosomal trafficking and genetic engineering. Key
techniques will include cell culture, lentiviral transduction and over-expression
analyses, transcriptomics, proteomics, bioinformatics and in vitro assays of EV
function.