title: Mesenchymal stromal cells as multifunctional cellular therapeutics - a potential role for extracellular vesicles.
abstract: Mesenchymal stromal cells (MSCs), multipotent cells present in tissues throughout the body, can reconstitute adipogenic, osteogenic and chondrogenic tissues, but are also of great interest as mediators of immune modulation and suppression. MSCs are able to improve transplant engraftment, treat graft versus host disease and suppress T cell responses and therefore have great potential as therapeutic agents. Their immune modulatory capacity is mediated through both cell-to-cell contact and cytokine secretion, but it is becoming clear that extracellular vesicles (EV) produced by MSC also possess immunomodulatory properties. These vesicles are easy to prepare and store, do not carry nuclear material and cannot form tumours, and therefore also represent a highly desirable therapeutic agent. This review outlines the formation and characterisation of extracellular vesicles, the reported function of MSC-EVs in vitro and in vivo, and addresses some of the emerging issues with nomenclature, EV therapeutic dose and tissue source. The development of GMP-grade production protocols and effective characterisation of MSC extracellular vesicles is essential to their successful use as immune modulating therapeutic agents, and this review outlines the current status of the research in this area.
authors.affiliation: Research Development and Innovation, Scottish National Blood Transfusion Service, Ellen's Glen Road, Edinburgh, UK. Electronic address: Jillian.Stephen1@nhs.net.
authors.forename: Jillian
authors.initials: J
authors.lastname: Stephen
authors.affiliation: Research Development and Innovation, Scottish National Blood Transfusion Service, Ellen's Glen Road, Edinburgh, UK.
authors.forename: Elena Lopez
authors.initials: EL
authors.lastname: Bravo
authors.affiliation: Research Development and Innovation, Scottish National Blood Transfusion Service, Ellen's Glen Road, Edinburgh, UK.
authors.forename: David
authors.initials: D
authors.lastname: Colligan
authors.affiliation: Research Development and Innovation, Scottish National Blood Transfusion Service, Ellen's Glen Road, Edinburgh, UK.
authors.forename: Alasdair R
authors.initials: AR
authors.lastname: Fraser
authors.affiliation: Research Development and Innovation, Scottish National Blood Transfusion Service, Ellen's Glen Road, Edinburgh, UK.
authors.forename: Juraj
authors.initials: J
authors.lastname: Petrik
authors.affiliation: Research Development and Innovation, Scottish National Blood Transfusion Service, Ellen's Glen Road, Edinburgh, UK.
authors.forename: John D M
authors.initials: JD
authors.lastname: Campbell
mesh_terms: D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D056747:Immunomodulation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines
keywords: Cellular therapy; Extracellular vesicles; Immune modulation; Mesenchymal stromal cells; T-cells