Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries

Mayo Clinic of Medicine, Rochester, Minn 55905, USA.
Stroke (Impact Factor: 6.02). 11/2004; 35(10):2378-84. DOI: 10.1161/01.STR.0000141893.33677.5d
Source: PubMed

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.

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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 [11] [12]. 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. "
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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 [25]. 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 [13], rabbit carotid artery injury [26], the porcine myocardial infarction [27], and murine retinal ischaemia [5]. 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. "
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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 [3]. 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 [4] [5]. However, the regulatory mechanisms of the biological properties of EPCs remain unclear, especially with respect to ion channels [6] [7]. "
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