Exosomes: A Tool for Bone Tissue Engineering

Abstract

Mesenchymal stem cells (MSCs) have been repeatedly shown to be a valuable source for cell-based therapy in regenerative medicine, including bony tissue repair. However, engraftment at the injury site is poor. Recently, it has been suggested that MSCs and other cells act through a paracrine signaling mechanism. Exosomes are nanostructures that have been implicated in this process. They carry DNA, RNA, proteins, and lipids and play an important role in cell-to-cell communication directly modulating their target cell at a transcriptional level. In a bone microenvironment, they have been shown to increase osteogenesis and osteogenic differentiation in vivo and in vitro. In the following review, we will discuss the most advanced and significant knowledge of biological functions of exosomes in bone regeneration and their clinical applications in osseous diseases. Impact statement Mesenchymal stem cells have been shown to be a promising tool in bone tissue engineering. Recently, it has been suggested that they secrete exosomes containing messenger RNA, proteins, and lipids, thus acting through paracrine signaling mechanisms. Considering that exosomes are nonteratogenic and have low immunogenic potential, they could potentially replace stem-cell based therapy and thus eradicate the risk of neoplastic transformation associated with cell transplantations in bone regeneration.

Keywords: bone defect; bone tissue engineering; exosomes; mesenchymal stromal cells; regenerative medicine.

FIG. 1.

Schematic of the biogenesis of exosomes. Invagination of the plasma membrane to form early endosomes. Involving the Golgi apparatus, DNA, RNA, proteins, and lipids are incorporated by invagination of the endosomal membrane to form late endosomes. A multivesicular body is formed containing multiple intraluminal vesicles. The multivesicular body is either processed by lysosomes for degradation or fuses with the cell plasma membrane to release the intraluminal vesicles, now called exosomes, into the extracellular space. This process is called exocytosis. ER, endoplasmatic reticulum; ILV, intraluminal vesicle; MVB, multivesicular body.