A limitation of using exosomes to their fullest potential is their limited secretion from cells, a major bottleneck to efficient exosome production and application. This is especially true for mesenchymal stem cells (MSCs), which can self-renew but have a limited expansion capacity, undergoing senescence after only a few passages, with exosomes derived from senescent stem cells showing impaired regenerative capacity compared to young cells.
Researchers from SUNY Buffalo and University of North Carolina at Chapel Hill examined the effects of small molecule modulators capable of enhancing exosome secretion from MSCs. The treatment of MSCs with a combination of N-methyldopamine and norepinephrine robustly increased exosome production by three-fold without altering the ability of the MSC exosomes to induce angiogenesis, polarize macrophages to an anti-inflammatory phenotype, or downregulate collagen expression. These small molecule modulators provide a promising means to increase exosome production by MSCs.
The effect of small molecule compounds on exosomal
production-related pathways after 48 h treatment
RT-PCR quantification of (A) nSMase2 (SMPD3), (B) Hrs, (C) Tsg101, (D) Stam1, (E) Alix, (F) microphthalmia-associated transcription factor (MITF), (G) Rab27a, and (H) Rab27b. One-way ANOVA with Dunnett’s multiple comparisons test, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001; n = 3–5.