Authors
Alejandro Toro-Rivera, Wendy V. Jaraba-Álvarez, Angélica M. Calle-Ramírez, Juan P. Franco-Salazar, Luz Adriana Palacio, Daniela Martínez-Penaloza, Julián España, Karolynn Halpert, Hector Ortega-Arellano and Víctor Gómez
Abstracts
Background: Degenerative disc disease (DDD) is a primary cause of chronic back pain and disability globally. Although Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs) possess proven therapeutic potential, the added clinical value of supplementing this treatment with their exosomal derivatives remains insufficiently defined in the literature. Methods: This study integrated the detailed proteomic characterization of these exosomes with clinical outcome analysis in a prospective cohort of 125 patients with thoracolumbar DDD treated intradiscally with WJ-MSCs alone or combined with exosomes. Exosomes were characterized using nanoparticle tracking analysis, flow cytometry, proteomics, and Gene Ontology enrichment analysis. Results: Proteomic profiling identified 1018 unique exosomal proteins significantly enriched in extracellular matrix organization, collagen and proteoglycan metabolism (highlighting structural effectors such as COL2A1 and lumican), proteolytic regulation (TIMP1, TIMP2, and CD109), and humoral immune and complement pathways (CD59 and SERPING1). Clinically, both treatment groups achieved significant reductions in pain and disability at 3 and 6 months compared to baseline. Supplementation with exosomes was not associated with clinically meaningful pain reduction at any follow-up (aRR = 0.836; 95% CI, 0.594–1.175; p = 0.3021). In contrast, WJ-MSCs plus exosomes were associated with a higher probability of clinically meaningful ODI improvement at any follow-up (aRR = 1.525; 95% CI, 1.075–2.162; p = 0.0180) and at 6 months (aRR = 2.003; 95% CI, 1.175–3.414; p = 0.0107). No serious adverse events were reported in either group. Conclusions: WJ-MSC-derived exosomes carry a multimodal protein cargo aligned with multiple biological processes involved in degenerative disc disease. Exosome supplementation was associated with greater functional improvement, but not pain reduction, supporting its potential role as a paracrine reinforcement strategy within WJ-MSC-based therapy and warranting further controlled translational studies.
