Advances in Mesenchymal Stem Cell-Derived Exosomes as Drug Delivery Vehicles.

Dingyu Rao,Tianyu Zhong,Zuxiong Zhang,Defa Huang,Zhixian Tang,Chengpeng Sang

doi:10.3389/fbioe.2021.797359

Abstract

Exosomes are tiny vesicles with a double membrane structure that cells produce. They range in diameter from 40 to 150 nm and may contain a variety of biomolecules including proteins and nucleic acids. Exosomes have low toxicity, low immunogenicity, and the ability to encapsulate a wide variety of substances, making them attractive drug delivery vehicles. MSCs secrete large amounts of exosomes and hence serve as an excellent source of exosomes. MSCs-derived exosomes have regenerative and tissue repair functions comparable to MSCs and can circumvent the risks of immune rejection and infection associated with MSC transplantation, indicating that they may be a viable alternative to MSCs’ biological functions. In this review, we summarized the drug delivery methods and advantages of exosomes, as well as the advancement of MSC exosomes as drug carriers. The challenges and prospects of using exosomes as drug delivery vectors are presented.

Highlights

Mesenchymal stem cells (MSCs) are a class of pluripotent stem cells capable of self-renewal and multidirectional differentiation
By analyzing CD81 levels, this study found that hESC-MSC produced at least 10-fold the amount of CD81 + exosomes produced by other cell lines (Yeo et al, 2013)
The findings indicate that MSCs-derived TNF-Related Apoptosis Induced Ligand (TRAIL)-loaded exosomes (Exo-TRAIL) inhibit melanoma progression by promoting massive necrosis of cancer cells and that their anti-tumor effect is dosedependent

Summary

INTRODUCTION

Mesenchymal stem cells (MSCs) are a class of pluripotent stem cells capable of self-renewal and multidirectional differentiation. Exosomes have been detected in a variety of body fluids, including blood, urine, breast milk, ascites, amniotic fluid, saliva, and cerebrospinal fluid (Wang et al, 2019) They can carry biologically active molecules such as nucleic acids and proteins and serve as messengers between cells, delivering their contents to the target cell (Hendrix et al, 2010; Gu et al, 2012; Weber et al, 2019). Because of its particle size advantage, it can transport cargo molecules across biological barriers (such as the blood-brain barrier) (Chen et al, 2016a) It is one of the best choices for researchers to find drug carriers in vivo (Lai et al, 2013). Studies have shown that MSC-Exos possesses anti-fibrotic, anti-inflammatory, and pro-angiogenic effects with regenerative potential in myocardial tissue from ischemic injury in chronic myocardial infarction, acute and chronic renal injury, and fibrotic tissue (Gatti et al, 2011; Li et al, 2013; Yamaguchi et al, 2015). Extracellular drug loading entails the purification and isolation of exosomes from donor cells followed by the loading of the desired drug into the exosomes using several methods such as incubation, FIGURE 2 | Exosomes extracellular drug delivery strategy. (A) Drug co-incubation; (B) Acoustic processing; (C) Squeeze method; (D) Electroporation; (E) Freezethaw; (F) Saponin-assisted loading

Method

DISCUSSION