Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries
ABSTRACT Circulating endothelial progenitor cells (EPCs) play an important role in repair of injured vascular endothelium and neovascularization. The present study was designed to determine the effect of EPCs transplantation on the regeneration of endothelium and recovery of endothelial function in denuded carotid arteries.
Isolated mononuclear cells from rabbit peripheral blood were cultured in endothelial growth medium for 7 days, yielding EPCs. A rabbit model of common carotid artery denudation by passage of a deflated balloon catheter was used to evaluate the effects of EPCs on endothelial regeneration and vasomotor function. Immediately after denudation, autologous EPCs (10(5) cells in 200 microL saline) or 200 microL saline alone (control) were administered into the lumen of injured artery.
Four weeks after transplantation, fluorescence-labeled colonies of EPCs were found in the vessel wall. Local transplantation of EPCs as compared with saline administration accelerated endothelialization and significantly improved endothelium-dependent relaxation when assessed 4 weeks after denudation (n=4 to 5, P<0.05). Transplantation of EPCs did not affect vasomotor function of arterial smooth muscle cells. Protein array analysis of conditioned media obtained from cultured EPCs demonstrated the ability of these cells to produce and release a number of proangiogenic cytokines.
We conclude that local delivery of cultured circulating EPCs into the lumen of denuded carotid arteries accelerates endothelialization and improves endothelial function. Paracrine effects of EPCs may contribute to regenerative properties of EPCs.
- SourceAvailable from: Daniel Ortega
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- "Several studies have demonstrated the reduction of restenosis after EPC delivery although primarily with initial cessation of blood flow for 20 min to increase cell attachment [11e13]. Delivered EPCs were found to speed up re-endothelisation via integration into the new endothelial layer  . A limited number of studies have assessed the effect of MSC delivery on endothelisation and restenosis, while no data is available for the effect of magnetic MSC delivery in this context. "
ABSTRACT: Vascular occlusion can result in fatal myocardial infarction, stroke or loss of limb in peripheral arterial disease. Interventional balloon angioplasty is a common first line procedure for vascular disease treatment, but long term success is limited by restenosis and neointimal hyperplasia. Cellular therapies have been proposed to mitigate these issues; however efficacy is low, in part due to poor cell retention. We show that magnetic targeting of mesenchymal stem cells gives rise to a 6-fold increase in cell retention following balloon angioplasty in a rabbit model using a clinically applicable permanent magnet. Cells labelled with superparamagnetic iron oxide nanoparticles exhibit no negative effects on cell viability, differentiation or secretion patterns. The increase in stem cell retention leads to a reduction in restenosis three weeks after cell delivery.Biomaterials 12/2012; 34:1987. DOI:10.1016/j.biomaterials.2012.11.040 · 8.31 Impact Factor
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- "Using rhesus monkey-derived OECs in this mouse experimental system, it was recently shown that there was a decreased potential to form functional capillaries with chronological age . Most importantly , it has been demonstrated that OECs directly incorporate into damaged ischaemic vasculature in vivo as reported using different animal models such as the murine hind limb ischaemia , rabbit carotid artery injury , the porcine myocardial infarction , and murine retinal ischaemia . For the specific purpose of vascular disease modelling, OECs should be the preferred EPC subtype to use, as they are currently the only EPCs with both great proliferative potential and unequivocal endothelial phenotype. "
ABSTRACT: Endothelial progenitor cells (EPCs) have great clinical value because they can be used as diagnostic biomarkers and as a cellular therapy for promoting vascular repair of ischaemic tissues. However, EPCs also have an additional research value in vascular disease modelling to interrogate human disease mechanisms. The term EPC is used to describe a diverse variety of cells, and we have identified a specific EPC subtype called outgrowth endothelial cell (OEC) as the best candidate for vascular disease modelling because of its high-proliferative potential and unambiguous endothelial commitment. OECs are isolated from human blood and can be exposed to pathologic conditions (forward approach) or be isolated from patients (reverse approach) in order to study vascular human disease. The use of OECs for modelling vascular disease will contribute greatly to improving our understanding of endothelial pathogenesis, which will potentially lead to the discovery of novel therapeutic strategies for vascular diseases.03/2012; 2012:346735. DOI:10.1155/2012/346735
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- "The traditional paradigm of vascular repair is based on the proliferation and migration of pre-existing mature endothelial cells from the adjacent vasculature . Recently, endothelial progenitor cells (EPCs), which can be mobilized and recruited into injured vessels, have become increasingly recognized to play a key role in the maintenance of vascular integrity and to act as ''repair " cells in response to vascular injury  . However, the regulatory mechanisms of the biological properties of EPCs remain unclear, especially with respect to ion channels  . "
ABSTRACT: Knockdown of stromal interaction molecule 1 (STIM1) significantly suppresses neointima hyperplasia after vascular injury. Endothelial progenitor cells (EPCs) are the major source of cells that respond to endothelium repair and contribute to re-endothelialization by reducing neointima formation after vascular injury. We hypothesized that the effect of STIM1 on neointima hyperplasia inhibition is mediated through its effect on the biological properties of EPCs. In this study, we investigated the effects of STIM1 on the proliferation and migration of EPCs and examined the effect of STIM1 knockdown using cultured rat bone marrow-derived EPCs. STIM1 was expressed in EPCs, and knockdown of STIM1 by adenoviral delivery of small interfering RNA (siRNA) significantly suppressed the proliferation and migration of EPCs. Furthermore, STIM1 knockdown decreased store-operated channel entry 48h after transfection. Replenishment with recombinant human STIM1 reversed the effects of STIM1 knockdown. Our data suggest that the store-operated transient receptor potential canonical 1 channel is involved in regulating the biological properties of EPCs through STIM1. STIM1 is a potent regulator of cell proliferation and migration in rat EPCs and may play an important role in the biological properties of EPCs.Biochemical and Biophysical Research Communications 07/2010; 398(2):315-20. DOI:10.1016/j.bbrc.2010.06.088 · 2.28 Impact Factor