Cardiomyocyte progenitor cell-derived exosomes stimulate migration of endothelial cells

Abstract

Patients suffering from heart failure as a result of myocardial infarction are in need of heart transplantation. Unfortunately the number of donor hearts is very low and therefore new therapies are subject of investigation. Cell transplantation therapy upon myocardial infarction is a very promising strategy to replace the dead myocardium with viable cardiomyocytes, smooth muscle cells and endothelial cells, thereby reducing scarring and improving cardiac performance. Despite promising results, resulting in reduced infarct size and improved cardiac function on short term, only a few cells survive the ischemic milieu and are retained in the heart, thereby minimizing long-term effects. Although new capillaries and cardiomyocytes are formed around the infarcted area, only a small percentage of the transplanted cells can be detected months after myocardial infarction. This suggests the stimulation of an endogenous regenerative capacity of the heart upon cell transplantation, resulting from release of growth factor, cytokine and other paracrine molecules by the progenitor cells – the so-called paracrine hypothesis. Here, we focus on a relative new component of paracrine signalling, i.e. exosomes. We are interested in the release and function of exosomes derived from cardiac progenitor cells and studied their effects on the migratory capacity of endothelial cells.

Exosomes as Biomarker Enriched Microvesicles: Characterization of Exosomal Proteins Derived from a Panel of Prostate Cell Lines with Distinct AR Phenotypes

“…For the purpose of this study we have simply confirmed the uptake of exosomes derived from DU145 prostate cancer cells into other PCa and benign cells and furthermore, transfer of exosomal CLU GFP derived from the LNCaP cell line to PC3 and LNCaP cells. Although more research is needed to investigate the mechanism involved in the uptake of exosomes by neighboring cells in the PCa microenvironment, our finding supports the previously hypothesized role of exosomes as cell-cell communication vesicles in tumor growth (54,55) cell migration (35,56,57), metastasis (58,59), and angiogenesis (60).…”

Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression

“…5A). Because secretion of some MMPs in association with membrane vesicles including exosomes has been described (23,24), reduced secretion of MMP9 in Rab27a-impaired cells could be due to reduced exosome secretion. However, by comparing the amount of MMP9 present in CM from 10 5 cells, with the same CM after successive ultracentrifugation to deplete exosomes, or with exosomes obtained from 5.10 6 cells, we showed that the vast majority of MMP9 is secreted by 4T1 (Fig.…”

Exosomes

“…61,72 Human cardiomyocyte progenitor cells have also been shown to release exosomes, which can stimulate the migration of microvascular endothelial cells. 74 In an interesting recent study, human umbilical vein endothelial cells subjected to shear stress were shown to release vesicles (exosomes or microvesicles) enriched in miR-143/145, which controlled target gene expression in cocultured smooth muscle cells. 46 Importantly, the released vesicles reduced atherosclerotic lesion formation in a mouse model of atherosclerosis.…”