Page 77 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine

Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the.. .

sphingomyelin ceramide and lipid raft proteins incorporation of all these proteins in exosomes is
(de Gassart et al. 2003) which enable protection thought to be controlled by lipid-dependent
of exosome’s cargo from degradative enzymes or mechanisms primarily by the activity of the
chemicals and facilitates uptake of exosome’scon- endosomal sorting complex required for transport
tent into target cells through endocytosis or mem- (ESCRT) (Colombo et al. 2014).
brane fusion regardless of biological barriers (Lai Exosome content may vary according to the
et al. 2011). MSC-derived exosomes express evo- physiological and pathological conditions of the
lutionary conserved set of proteins including tissue microenvironment in which engrafted MSC
tetraspanins (CD81 CD63 CD9-involved in MSC is exposed. In this regard, the exosomal cargo can
proliferation and signaling) heat-shock proteins reveal the state of the donor MSC and can also
(HSP60 HSP70 HSP90-involved in MSC respond influence in a paracrine and/or endocrine manner
to stress) ALG-2-interacting protein X (Alix- the fate of the recipient cell (Schey et al. 2015;
apoptosis regulating protein) tumor susceptibility Villarroya-Beltri et al. 2014). The reliability of
gene 101 (TSG101-having role in cell growth and intercellular communication between MSC and
proliferation) and adhesion molecules (CD29 target cell is maintained and translated by specific
CD44,CD73- enabling migration of exosomes to components within the MSC-derived exosomes.
the inflamed and injured tissues) (Fig. 1). The These components are generally made of

Fig. 1 MSC-derived exosomes: morphology and into target cells through endocytosis or membrane fusion,
structure. MSC-derived exosomes are nano-sized extra- regardless of biological barriers. MSC-derived exosomes
cellular vesicles which are released from MSCs into the express evolutionary conserved set of proteins, including
extracellular milieu and taken up by target cells. Their tetraspanins (CD81, CD63, CD9), heat-shock proteins
membranes are enriched in cholesterol, sphingomyelin, (HSP60, HSP70, HSP90), and adhesion molecules
ceramide and lipid raft proteins which enable protection (CD29, CD44,CD73) and carry nucleic acids, proteins
of exosome’s cargo from degradative enzymes or (cytokines, chemokines) and lipids having important role
chemicals and facilitates uptake of exosome’s content in immunomodulation and tissue regeneration