Exosomes from Human CD34+ Stem Cells Mediate their Pro-angiogenic Paracrine Activity

By S. Sahoo, Ekaterina Klychko, T. Thorne, S. Misener, K. Schultz, Meredith Millay, A. Ito, Ting Liu, C. Kamide, Hemant Agrawal and 4 more. Circulation Research, 2011

600 citations recorded by the source corpus.

Rationale: Transplantation of human CD34+ stem cells to ischemic tissues has been associated with reduced angina, improved exercise time, and reduced amputation rates in phase 2 clinical trials and has been shown to induce neovascularization in preclinical models. Previous studies have suggested that paracrine factors secreted by these proangiogenic cells are responsible, at least in part, for the angiogenic effects induced by CD34+ cell transplantation. Objective: Our objective was to investigate the mechanism of CD34+ stem cell–induced proangiogenic paracrine effects and to examine if exosomes, a component of paracrine secretion, are involved. Methods and Results: Exosomes collected from the conditioned media of mobilized human CD34+ cells had the characteristic size (40 to 90 nm; determined by dynamic light scattering), cup-shaped morphology (electron microscopy), expressed exosome-marker proteins CD63, phosphatidylserine (flow cytometry) and TSG101 (immunoblotting), besides expressing CD34+ cell lineage marker protein, CD34. In vitro, CD34+ exosomes replicated the angiogenic activity of CD34+ cells by increasing endothelial cell viability, proliferation, and tube formation on Matrigel. In vivo, the CD34+ exosomes stimulated angiogenesis in Matrigel plug and corneal assays. Interestingly, exosomes from CD34+ cells but not from CD34+ cell–depleted mononuclear cells had angiogenic activity. Conclusions: Our data demonstrate that human CD34+ cells secrete exosomes that have independent angiogenic activity both in vitro and in vivo. CD34+ exosomes may represent a significant component of the paracrine effect of progenitor cell transplantation for therapeutic angiogenesis.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e13072e41ebdc10ed81d3ada84a230eb1ea21f78

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Citations in the corpus

Exosome Theranostics: Biology and Translational Medicine (2018, background): “These vesicles accumulate in late endosomes by the inward budding of the early endosomal membrane and cytosol sequestration, thus transforming endosomes into multivesicular bodies (MVBs) (Figure 2F) [37].”
Exosomes as Critical Agents of Cardiac Regeneration Triggered by Cell Therapy (2014, result): “Transmission electron microscopy revealed most exosomes to be 30–90 nm in diameter, although smaller and larger particles were also present (Figures 1E and 1F), consistent with reports of exosomes derived from vascular cells (Hergenreider et al., 2012; Sahoo et al., 2011).”
Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. (2014, background): “EVs secreted by normal human dermal fibroblasts (NHDFs) lacked these beneficial effects, supporting the concept that functional activities of EVs depend on the parent cell.(17) A comparison of the miRNA transcriptional profile of EVs secreted by CPCs with that of EVs secreted”
Classification, Functions, and Clinical Relevance of Extracellular Vesicles (2012, background): “Thus, exosomes have an angiogenic activity in vitro and in vivo (Lai et al., 2010; Sahoo et al., 2011).”
Exosomes: vehicles of intercellular signaling, biomarkers, and vectors of cell therapy. (2015, background): “Furthermore, exosomes isolated from conditioned media (CM) of CD34+ stem cells have proangiogenic activity in vitro and in vivo (56).”