Exosome Therapy: A Promising Avenue for Treating Intervertebral Disc Degeneration

Abstract

Background: The human spine relies on intervertebral discs (IVDs) for support and mobility, functioning as shock absorbers that enable friction-free movement. However, IVDs are susceptible to degeneration (IVDD) due to age, excessive strain, and genetic factors, resulting in bulging or herniation that causes pain, stiffness, and nerve compression.

Current treatments: Current treatments primarily focus on symptom management through medication, physical therapy, or surgery in severe cases, without addressing tissue repair.

Emerging therapies: Exosome therapy has recently emerged as a promising regenerative approach for IVDD. Exosomes are small, membrane-bound vesicles released by cells, acting as messengers to transport proteins and RNA that influence recipient cell behavior.

Potential and challenges: Researchers are investigating exosomes for IVDD because they may promote disc repair and regeneration by delivering molecules that stimulate tissue recovery and carry anti-inflammatory agents to reduce inflammation and modulate pain. Engineering strategies, such as loading exosomes with therapeutic cargo or targeting molecules, can further enhance their efficacy. While exosome therapy for IVDD is still in early research stages, ongoing studies are promising, though challenges remain in optimizing isolation methods and ensuring clinical safety.

Conclusion: Exosome-based therapies could offer a safe, effective, and minimally invasive solution for individuals affected by IVDD.

Keywords: Exosome therapy; Intervertebral disc degeneration; Nucleus pulposus; Spinal cord injury; Stem cells.

Fig. 1

Sources of exosomes and their associated cell sizes in relation to exosome dimensions. Exosomes, nanosized extracellular vesicles ranging from 30 to 150 nm, are secreted by various cell types and play a crucial role in intercellular communication. This figure illustrates the diverse biological sources of exosomes, including adipose stem cells (15–30 µm), neural stem cells (10–20 µm), umbilical cord cells (15–25 µm), nucleus pulposus cells (10–20 µm), platelets (2–3 µm), bone marrow stem cells (15–30 µm), placental cells (15–30 µm), and endometrial cells (10–30 µm). The inclusion of cell sizes provides context for understanding the relative scale difference between the originating cells and the exosomes they produce, emphasizing the nanoscale size of exosomes compared to their parent cells. This comparison underscores the precision and efficiency of exosome-mediated signaling despite their small size relative to the source cells. (made from Biorender)

Fig. 2

This schematic illustrates how exosomes derived from various cell types-including nucleus pulposus cells, notochordal cells, and mesenchymal stem cells from bone marrow, adipose tissue, umbilical cord, and placenta-modulate key processes in IVDD. Through delivery of miRNAs and proteins, these exosomes regulate extracellular matrix homeostasis, inhibit apoptosis, reduce inflammation, suppress ER stress, and promote regeneration of disc cells, collectively contributing to the attenuation of IVDD progression and offering promising therapeutic potential. Adapted from "Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration" by Li et al., 2022, Frontiers in Cell and Developmental Biology, CC BY 4.0. https://doi.org/10.3389/fcell.2021.822149

Fig. 3

The figure depicts exosome biogenesis, highlighting the formation and encapsulation of miRNAs. The process begins with endocytosis, followed by the formation of early and late endosomes, which mature into multivesicular bodies. These bodies then release exosomes containing specific miRNAs, such as miR-145 and miR-532-5p, which target IVDD. (made from Biorender)

Fig. 4

Schematic representation of the role of exosomes from various sources in IVD homeostasis and degeneration. Exosomes deliver miRNAs to NP cells, ECM synthesis and inhibiting its degradation. Under mechanical load and inflammatory conditions, exosomes modulate immune responses, suppress vascularization, and reduce macrophage infiltration, thereby preserving the immune privilege of the disc. These processes help maintain normal IVD structure and function, highlighting the therapeutic potential of exosome-based approaches for preventing or reversing disc degeneration. Adapted from Li et al., 2022, Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration, Frontiers in Cell and Developmental Biology, CC BY 4.0. https://doi.org/10.3389/fcell.2021.822149

Fig. 5

Exosome engineering strategies for IVDD therapy. The depicted strategies include: (1) direct loading of exosomes with therapeutic cargo, such as nucleic acids or proteins, enabling targeted delivery of specific molecules; (2) inducing mutations in cells to produce engineered exosomes with enhanced therapeutic properties; (3) loading exosomes into biomaterials for sustained release and localized delivery; (4) fusion of functional lipid molecules to engineer the exosome membrane for improved targeting and drug delivery; and (5) direct injection of engineered exosomes for minimally invasive IVDD therapy. (made from Biorender)