Current Knowledge and Future Perspectives on Mesenchymal Stem Cell-Derived Exosomes as a New Therapeutic Agent

Hyeon Su Joo, Ju Hun Suh, Hyeon Ji Lee, Eun Song Bang, Jung Min Lee, Hyeon Su Joo, Ju Hun Suh, Hyeon Ji Lee, Eun Song Bang, Jung Min Lee

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.

Keywords: exosome; mesenchymal stem cell; pre-conditioning; translational medicine.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results

Figures

Figure 1
Figure 1
Exosome biogenesis and its application. (A) Exosome biogenesis. Three pathways for exosome biogenesis. (❶) ESCRT-dependent pathway and related proteins, (❷) ESCRT-independent pathway and related proteins, (❸) Direct budding of plasma membrane and related proteins. (B) Exosome components. MFGE8: milk fat globule-EGF factor 8 protein; ICAM-1: intercellular adhesion molecule 1; LAMP1,2: lysosomal-associated membrane protein 1,2; MHC I, II: major histocompatibility complex I, II. MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; PGK1: phosphoglycerate kinase 1. (C) Applications of exosomes. (①) Drug delivery: Therapeutic agents such as chemicals, peptides, and siRNAs can be delivered into patients. (②) Diagnosis: Exosomes derived from patients can be used for disease diagnosis. (③) Therapy: Exosomes derived from MSCs can be used to treat several diseases.
Figure 2
Figure 2
Pre-conditioning approaches for MSC to enhance the secretion and therapeutic efficacy of exosomes. LPS: lipopolysaccharides; NO: nitric oxide; DFO: deferoxamine; IFN: interferon; TNF: tumor necrosis factor; IL: interleukin; TGF: transforming growth factor; IDO: indoleamine-pyrrole 2,3-dioxygenase; HIF: hypoxia-inducible factors; miRNAs: micro RNAs; UV: ultraviolet.

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