Hydrogel-Loaded Exosomes: A Promising Therapeutic Strategy for Musculoskeletal Disorders

Table 5

Summary of the efficacy and mechanism of cartilage repair by EVs from different sources of MSCs.

EVs source	Main mechanism	Proliferative effect	Ease of preparation	References
Human embryonic stem cells MSC (hESC-MSC)	Inducing phosphorylation of AKT and ERK and activates the AKT/ERK signaling pathway via CD73/ecto-50 nuclease activity	+++	√	[364, 365]
Bone marrow MSCs (BMSCs)	Inducing phosphorylation of AKT and ERK and activates the AKT/ERK signaling pathway via CD73/ecto-50 nuclease activity	++	×	[366, 367]
	Inducing the expression of chondrocyte markers (col II, aggregated proteoglycans) while inhibiting catabolism (MMP-13, AD⁃AMTS5) and inflammatory markers (iNOS)
Syno vial-derived MSC (SMSC)	Carrying Wnt5a and Wnt5b that activate transcriptional coactivator-associated protein (yes-associated protein, YAP) via alternative Wnt-signaling pathways and enhancing proliferation and migration of articular chondrocytes. But extracellular matrix secretion is significantly reduced and miR-140-5p needs to be packaged to suppress this side effect via RalA	++	×	[368, 369]
Infrapatellar fat pad-derived MSC (MSCIPFP)	Protecting cartilage from OA by inhibiting chondrocyte apoptosis and balancing anabolic and catabolic processes, possibly associated with miR-100-5p-mediated inhibition of the mTOR autophagic pathway	++++	√	[370, 371]
Adipose-derived MSC (AD-MSC)	Reducing the production of the inflammatory factors TNF-α, IL-6, and IL-10 in chondrocytes, thereby reducing ACD and preventing the development of OA	++	√	[372, 373]
	Reducing c-jun, which further reduces the DNA binding affinity of AP-1 and NF-κB and thus decreases MMP-13 expression
	Prdx6 mediates cartilage antioxidant and protective effects