title: The stem cell secretome and its role in brain repair.
abstract: Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS.
authors.affiliation: CNS Repair Unit, Institute of Experimental Neurology, Division of Neurosciences, San Raffaele Scientific Institute, 20132 Milan, Italy; Biomolecular Mass Spectrometry Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy. Electronic address: drago.denise@hsr.it.
authors.forename: Denise
authors.initials: D
authors.lastname: Drago
authors.forename: Chiara
authors.initials: C
authors.lastname: Cossetti
authors.forename: Nunzio
authors.initials: N
authors.lastname: Iraci
authors.forename: Edoardo
authors.initials: E
authors.lastname: Gaude
authors.forename: Giovanna
authors.initials: G
authors.lastname: Musco
authors.forename: Angela
authors.initials: A
authors.lastname: Bachi
authors.forename: Stefano
authors.initials: S
authors.lastname: Pluchino
mesh_terms: D000818:Animals; D001921:Brain; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D019899:Paracrine Communication; D020543:Proteome / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells
chemical_list: D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors; D020543:Proteome
keywords: Brain repair; Mesenchymal stem cells; Neural stem cells; Secretome; Stem cell transplantation