J Korean Orthop Assoc.  2025 Mar;60(1):1-10. 10.4055/jkoa.2025.60.1.1 .

Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles for Disc Degeneration

Affiliations
  • 1Department of Orthopaedic Surgery, Yeungnam University College of Medicine, *Laboratory of Veterinary Tissue Engineering, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea

Abstract

Intervertebral disc degeneration is associated with diverse spine diseases, including spinal stenosis, facet arthropathy, and disc herniation, which have socio-economic effects. A normal intervertebral disc has consistency and homeostasis, consisting of annulus fibrosus, nucleus pulposus, notochordal cells, nucleus pulposus cells, and an endplate with an immune privilege. On the other hand, when the degenerative process has pathologic causes, the inflammatory reaction could lead to nerve sprouting and vascularization into the tissue. Histopathologically, the pathologic process involves the degradation of the extracellular matrix, apoptosis and necrosis of nucleus pulposus cells, inhibition of chondrogenic differentiation, disruption of endplate chondrogenic cells, and other processes. Various approaches for managing disc degeneration have been reported. Among them, mesenchymal stem cells (MSCs) have been regarded as representative trials. In vitro and animal studies with MSCs have reported some promising outcomes in terms of inflammatory modulation and regeneration, but several limitations have been pointed out, including the issues of graft rejection and survival. Because the paracrine mechanism would be a main therapeutic factor of MSCs, extracellular vesicles (EVs), one of the factors released from MSCs, have been considered a promising source for regenerative medicine. EVs possess nucleic acids, functional proteins, and inflammation-related factors, playing a significant role in the inflammatory reaction and regeneration. The current review article discusses the pathophysiology of disc degeneration, outcomes of conventional MSCs and EVs, and current limitations and future perspectives on EV therapeutics.

Keyword

extracellular vesicle; mesenchymal stem cell; intervertebral disc; degeneration; therapeutics
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