Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated difficulties and opportunities. either a paracrine effect or a direct cell-to-cell interaction, or MSCs may induce host cells to secrete bioactive factors, which promote survival and proliferation of the parenchymal cells (brain remodeling) and thereby improve functional recovery. It is well GW4064 manufacturer documented that this predominant mechanisms by which MSCs promote brain remodeling and functional recovery after brain injury are related to bioactive factors secreted from MSCs or from parenchymal cells stimulated by MSCs (Chen et al., 2002; Mahmood et al., 2004). Much of research on MSC secretion has centered on individual small molecules such as growth factors, chemokines and cytokines. Paradigm-shifting findings that therapeutic effects of MSCs are mediated by secreted factors as opposed to the previous notion of differentiation into hurt tissues offer numerous possibilities for ongoing therapeutic development of MSC secreted products. MSC-derived Exosome as a Novel Therapy for TBI Recent GW4064 manufacturer studies show that therapeutic effects of MSCs are likely attributed to their strong generation and release of exosomes (Lai et al., 2010; Xin et al., 2013; Zhang et al., 2015). Exosomes are endosome-derived small membrane vesicles, approximately 30 to 100 nm in diameter, and are released into extracellular fluids by cells in all living systems. Administration of cell-free exosomes derived from MSCs is sufficient to exert therapeutic effects of intact MSCs after brain injury (Xin et al., 2013; Zhang et al., 2015, 2016). A recent statement demonstrates that extracellular vesicles (EVs) from MSCs are not inferior to MSCs in a rodent stroke model by comparing therapeutic efficacy of MSC-EVs with that of MSCs (Doeppner et al., 2015). The exosomes transfer RNAs and proteins to other cells which then act epigenetically to alter the function of the recipient cells. The development of cell-free exosomes derived from MSCs for treatment of TBI is just in its infancy (Zhang et al., 2015, 2016; Goat polyclonal to IgG (H+L)(PE) Kim et al., 2016). In a proof-of-principle study, an intravenous delivery of MSC-derived exosomes enhances functional recovery and promotes neuroplasticity in young adult male rats subjected to TBI induced by controlled cortical impact (Zhang et al., 2015), as shown in Physique 1. A recent study also exhibited that isolated extracellular vesicles from MSCs reduce cognitive impairments in a mouse model of TBI (Kim et al., 2016). Administration of cell-free nanosized exosomes may avoid potential issues associated with administration of living cells, which can replicate. Compared to their parent cells, exosomes may have a superior GW4064 manufacturer security profile, they do not replicate or induce microvascular embolism, and can be safely stored without losing function. Exosomes could substitute for the whole cell therapy in the treatment of TBI. This may open new clinical applications for off-the-shelf interventions with MSC-derived exosomes for TBI. MSCs are most typically produced in traditional 2 dimensional (2D) adherent cell culture. Three dimensional (3D) conditions such as spheroid culture have been shown to stimulate higher levels of trophic factor secretion GW4064 manufacturer compared to monolayer culture. MSCs seeded in the 3D collagen scaffolds generated significantly more exosomes compared to the MSCs cultured in the 2D standard condition (Zhang et al., 2016). Exosomes derived from MSCs cultured in 3D scaffolds provided better end result in.