Potential Therapeutic Applications of Exosomes in Bone Regenerative Medicine

Abstract

The ability of bone regeneration is relatively robust, which is crucial for fracture healing, but delayed healing and nonunion are still common problems in clinical practice. Fortunately, exciting results have been achieved for regenerative medicine in recent years, especially in the area of stem cell-based treatment, but all these cell-based approaches face challenging problems, including immune rejection. For this reason, exosomes, stem cell-derived small vesicles of endocytic origin, have attracted the attention of many investigators in the field of bone regeneration. One of the attractive features of exosomes is that they are small and can travel between cells and deliver bioactive products, including miRNA, mRNA, proteins, and various other factors, to promote bone regeneration, with undetectable immune rejection. In this chapter, we intend to briefly update the recent progressions, and discuss the potential challenges in the target areas. Hopefully, our discussion would be helpful not only for the clinicians and the researchers in the specific disciplines but also for the general audiences as well.

Osteoblastogenesis Alters Small RNA Profiles in EVs Derived from Bone Marrow Stem Cells (BMSCs) and Adipose Stem Cells (ASCs)

“…Multipotent stem cells (MSCs) are stem cells capable of self-renewal and differentiation into a variety of cell types, including osteoblasts, chondrocytes, and adipocytes, that are important for tissue regeneration and repair [ 1 , 2 ]. There are two mechanisms linked to the potential therapeutic function of MSCs: differentiation to target cells and the release of paracrine factors [ 3 ]. One subset of the paracrine factors secreted by MSCs are the exosomes–a class of extracellular vesicles (EVs) that are formed in the endosomal compartment and secreted when multivesicular bodies (MVBs) fuse with the plasma membrane [ 3 , 4 ].…”

“…There are two mechanisms linked to the potential therapeutic function of MSCs: differentiation to target cells and the release of paracrine factors [ 3 ]. One subset of the paracrine factors secreted by MSCs are the exosomes–a class of extracellular vesicles (EVs) that are formed in the endosomal compartment and secreted when multivesicular bodies (MVBs) fuse with the plasma membrane [ 3 , 4 ]. EVs carry proteins and RNAs that can be taken up by recipient cells to allow cell-to-cell signaling in a paracrine manner [ 4 , 5 , 6 , 7 ].…”

“…Studies have shown that ASCs can differentiate into many different lineages, including osteoblastogenesis [ 28 ]; however, there is a high tendency for ASCs to spontaneously differentiate into adipocytes [ 2 ]. EVs derived from both BMSCs and ASCs have been shown to promote bone regeneration [ 3 , 29 , 30 , 31 , 32 , 33 , 34 ]. In addition, Baglio et al found that tRNA-derived RNA fragments were enriched in BMSC- and ASC-exosomes and that the small RNA expression profile in the exosomes was dependent on MSC tissue origin [ 1 ].…”

Effect of Amlodipine and l-Carnitin Separately and Collectively on Certain Body Parameters that Are Related to Bone Metabolism in Ovariectomized Albino Rats

“…Osteocalcin is a small g-carboxyglutamate protein secreted from osteoblasts and osteoclasts and is also expressed and secreted in bone marrow and many organs (37) . Osteocalcin acts as a regulator of bone mineralization, which is commonly used as a clinical marker of bone formation (38) .…”