Peripheral ischemia as a result of occlusive vascular disease is a widespread problem in patients over the age of 65. Angiogenic therapies that can induce microvascular growth have great potential for providing a long lasting solution for patients with ischemia and would provide and an appealing alternative to surgical and percutaneous interventions. However, many angiogenic therapies have seen poor efficacy in clinical trials, suggesting that patients with long term peripheral ischemia have considerable therapeutic resistance to angiogenic stimuli. Glioblastoma is one of the most angiogenic tumor types, inducing robust vessel growth in the area surrounding the tumor. One major angiogenic mechanism used by the tumor cells to induce blood vessel growth is the production of exosomes and other extracellular vesicles that can carry pro-angiogenic and immunomodulatory signals.
Here, researchers from the University of Texas at Austin explored whether the pro-angiogenic aspects of glioblastoma-derived exosomes could be harnessed to promote angiogenesis and healing in the context of peripheral ischemic disease. They demonstrate that the exosomes derived from glioblastoma markedly enhance endothelial cell proliferation and increase endothelial tubule formation in vitro. An analysis of the microRNA (miRNA) expression using next generation identified that exosomes contained a high concentration of miR-221. In addition, the researchers found that glioblastoma exosomes contained significant amounts of the proteoglycans glypican-1 and syndecan-4, which can serve as co-receptors for angiogenic factors including FGF-2. In a hindlimb ischemia model in mice, they found that the exosomes promoted enhanced revascularization in comparison to control alginate gels and FGF-2 treatment alone. Taken together, these results support that glioblastoma-derived exosomes have powerful effects in increases revascularization in the context of peripheral ischemia.
Characterization of exosomes isolated from glioblastoma cell line
(A) Cryo‐electron microscopy of isolated exosomes and microvesicles. Bar = 100 nm. (B) Size distribution of isolated vesicles from cultured glioblastoma cells measured by dynamic light scattering. (C) Protein concentration of syndecan‐4 (SDC4) and glypican‐1 (GPC1) in the exosomes.