A study of MSC Exosomes in Autoimmune Diseases

Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Ace Card to Address Autoimmune Diseases

Abstract
With the development of novel treatments for autoimmune disorders, it has become a popular research focus which mesenchymal stem cells (MSCs) have the capacity to counteract with autoimmune diseases progression. One of the underlying mechanisms behind their activities is the release of extracellular vesicles, especially exosomes. MSC-derived exosomes are hypoimmunogenic nanocarriers which contain numerous immunoregulatory factors and similar to other exosomes, are able to pass through boundaries like the blood-brain barrier (BBB). Accumulating evidence provided by animal studies has demonstrated that MSC-derived exosomes, as a novel therapy, can re-induce self-tolerance, without subsequent complications reported for other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases. Here, we briefly describe the biological characteristics of MSC-derived exosomes and review the experimentally verified outcomes for autoimmune disease therapy purposes.

Introduction
Mesenchymal stem cells (MSCs) are multipotent, self renewable, and spindle shape cells (1) which were firstly isolated from guinea-pig bone marrow and spleen by Friedenstein et al. in 1970 (2). Now, MSCs can be isolated from cord blood, umbilical cord, bone marrow, adipose tissue, and many other tissues (3, 4). The single connecting
feature of all these tissues is the presence of perivascular space around the blood vessels where pericytes come off and differentiate into MSCs after vessels got inflamed or injured. According to their common origin, pericytes and MSCs both are negative for CD34, CD45, CD56 and positively express CD29, CD44, CD73, CD90, CD105, CD146 (5-7). MSCs are functionally defined based on their capacity to produce molecules that provide a regenerative and immunoregulatory milieu. Moreover, these multipotent
cells can differentiate into a closely related family of cells in vitro or following transplantation and subsequently recover the damages. However, recent findings have reported that MSCs do not significantly differentiate into other lineages in vivo under normal condition (8). Consequently, in a new paradigm, Arnold Caplan coined
“Medical Signaling Cell” for MSCs to precisely express that mesenchymal stem cells dock at the sites of injury and produce regenerative and immunoregulatory components
(9, 10). Afterwards, a great number of clinical trials

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