Abstract
Mesenchymal stem cells (MSCs) are on the cusp of regenerative medicine due to their differentiation capacity, favorable culture conditions, ability to be manipulated in vitro, and strong immunomodulatory activity. Recent studies indicate that the pleiotropic effects of MSCs, especially their immunomodulatory potential, can be largely attributed to paracrine factors. Exosomes, vesicles that are 30-150 nanometers in diameter that function in cell-cell communication, are one of the key paracrine effectors. MSC-derived exosomes are enriched with therapeutic miRNAs, mRNAs, cytokines, lipids, and growth factors. Emerging evidences support the compelling possibility of using MSC-derived exosomes as a new form of therapy for treating several different kinds of disease such as heart, kidney, immune diseases, neural injuries, and neurodegenerative disease. This review provides a summary of current knowledge and discusses engineering of MSC-derived exosomes for their use in translational medicine.
Highlights
Mesenchymal stem cells (MSCs) have generated enormous interest in the field of regenerative medicine due to their ability to undergo multilineage differentiation, their favorable characteristics for culture and manipulation in vitro, and their strong immunomodulatory activity [1]
Exosome biogenesis occurs in early endosomes via the inward budding of the endosomal membrane to form intraluminal vesicles (ILVs), generating multivesicular bodies (MVBs) (Figure 1)
Hypoxia-pre-conditioned MSC-derived exosomes ameliorated cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice, a model of Alzheimer’s disease [71]. These results suggest that treatment with MSC-derived exosomes could improve disease phenotypes in human patients with neurodegenerative conditions
Summary
Mesenchymal stem cells (MSCs) have generated enormous interest in the field of regenerative medicine due to their ability to undergo multilineage differentiation, their favorable characteristics for culture and manipulation in vitro, and their strong immunomodulatory activity [1]. Recent studies suggest that the therapeutic effects of MSCs, especially those that are immunomodulatory, can be largely attributed to paracrine effectors [11]. These studies showed that MSCs do not engraft and replace damaged tissues directly. The paracrine effectors secreted by these cells exert therapeutic effects. Among such effectors, exosomes are considered key [11], having strong anti-inflammatory potential [12]. We will summarize important points about the characteristics, isolation, and therapeutic applications of MSC-derived exosomes, as well as methods to increase their therapeutic potential through pre-conditioning of MSC cultures. We will provide a perspective on the future of MSC-derived exosomes in translational medicine
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