Potential of Exosomes for Diagnosis and Treatment of Joint Disease: Towards a Point-of-Care Therapy for Osteoarthritis of the Knee

Abstract

In the knee joint, articular cartilage injury can often lead to osteoarthritis of the knee (OAK). Currently, no point-of-care treatment can completely address OAK symptoms and regenerate articular cartilage to restore original functions. While various cell-based therapies are being developed to address OAK, exosomes containing various components derived from their cells of origin have attracted attention as a cell-free alternative. The potential for exosomes as a novel point-of-care treatment for OAK has been studied extensively, especially in the context of intra-articular treatments. Specific exosomal microRNAs have been identified as possibly effective in treating cartilage defects. Additionally, exosomes have been studied as biomarkers through their differences in body fluid composition between joint disease patients and healthy subjects. Exosomes themselves can be utilized as a drug delivery system through their manipulation and encapsulation of specific contents to be delivered to specific cells. Through the combination of exosomes with tissue engineering, novel sustained release drug delivery systems are being developed. On the other hand, many of the functions and activities of exosomes are unknown and challenges remain for clinical applications. In this review, the possibilities of intra-articular treatments utilizing exosomes and the challenges in using exosomes in therapy are discussed.

Keywords: cartilage regeneration; exosome; osteoarthritis of the knee; point-of-care therapy.

Figure 1

Formation of exosomes and uptake into target cells. Early endosomes are formed by endocytosis and they transition to late endosomes. These are called multivesicular bodies (MVBs), with intraluminal membrane vesicles (ILVs). ILVs that are released from MVBs into the extracellular space are called exosomes. Released exosomes are taken up by the target cells through endocytosis, interactions with receptors on the cell membrane, or direct fusion with the cell membrane.

Figure 2

Structure of exosomes. Exosomes have a lipid bilayer membrane composed of lipid raft constituents, tetraspanins (such as CD9, 63 and 81), and proteins (such as integrin, cell specific receptors, MHC class I and class II, and flottilin-1). Exosomes contain cellular components such as proteins, DNA, mRNAs, miRNAs, proteins associated with MVB formation (ALIX, TSG101), and heat shock proteins (Hsp70, Hsp90).

Figure 3

Intra-articular treatments utilizing modified exosomes as a drug delivery system. The loading of specific components into exosomes can be conducted either before exosome isolation (pre-loading method) or after exosome isolation (post-loading method).