Abstract
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. Here, we 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.
Highlights
Exosomes are nanosized (30–150 nm) extracellular vesicles released by almost all cell types and are critical in mediating cell–cell communication [1,2]
The small molecule modulators were selected from a recent screening in prostate cancer cells [25]
To determine a range of non-toxic concentrations, mesenchymal stem cells (MSCs) were treated with the five different compounds at concentrations between 10 and 100 μM
Summary
Exosomes are nanosized (30–150 nm) extracellular vesicles released by almost all cell types and are critical in mediating cell–cell communication [1,2]. Mesenchymal stem cell (MSC)-derived exosomes have been shown to mediate tissue regeneration in a variety of diseases, including ischemic heart disease, lung injury, liver fibrosis, and cerebrovascular disease [7,8]. This is mainly due to their intrinsic regenerative capacity, in that they are able to induce angiogenesis, promote proliferation, prevent apoptosis, and inhibit inflammatory reactions [9]. In addition to their intrinsic biological functions, exosomes are promising drug carriers due to their small size, excellent biocompatibility, and capacity to load specific and diverse therapeutic molecules including proteins, nucleic acids, and small molecules
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