He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZSTransplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke 35:2378-2384

Mayo Clinic of Medicine, Rochester, Minn 55905, USA.
Stroke (Impact Factor: 5.72). 11/2004; 35(10):2378-84. DOI: 10.1161/01.STR.0000141893.33677.5d
Source: PubMed


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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    • "The in vivo repair of the endothelium is mediated by endothelial progenitor cells (EPCs, characterized by the expression of CD34 marker among other markers [25]). The EPCs migrate to the sites of endothelial injury, incorporate in the endothelium and differentiate into ECs [26], [27]. Experimental results show that EPCs participate in neovascularization processes in the adult brain of mice after ischemia [28]. "
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    ABSTRACT: The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.
    PLoS ONE 06/2014; 9(6):e99733. DOI:10.1371/journal.pone.0099733 · 3.23 Impact Factor
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    • "The endothelium has regenerative capabilities that offer protection against atherosclerosis. It is believed that the damaged endothelium can not only be repaired by the proliferation and migration of neighboring endothelial cells, but also by endothelial progenitor cells (EPCs) [1], [2]. EPCs are mobilized from bone marrow, migrate to ischemic tissue, and contribute to ischemia-induced neovascularization [3]. "
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    ABSTRACT: Dysfunction of endothelial progenitor cells (EPCs) contributes to diabetic vascular disease. MicroRNAs (miRs) have emerged as key regulators of diverse cellular processes including angiogenesis. We recently reported that miR-126, miR-130a, miR-21, miR-27a, and miR-27b were downregulated in EPCs from type II diabetes mellitus (DM) patients, and downregulation of miR-126 impairs EPC function. The present study further explored whether dysregulated miR-130a were also related to EPC dysfunction. EPCs were cultured from peripheral blood mononuclear cells of diabetic patients and healthy controls. Assays on EPC function (proliferation, migration, differentiation, apoptosis, and colony and tubule formation) were performed. Bioinformatics analyses were used to identify the potential targets of miR-130a in EPCs. Gene expression of miR-103a and Runx3 was measured by real-time PCR, and protein expression of Runx3, extracellular signal-regulated kinase (ERK), vascular endothelial growth factor (VEGF) and Akt was measured by Western blotting. Runx3 promoter activity was measured by luciferase reporter assay. A miR-130a inhibitor or mimic and lentiviral vectors expressing miR-130a, or Runx3, or a short hairpin RNA targeting Runx3 were transfected into EPCs to manipulate miR-130a and Runx3 levels. MiR-130a was decreased in EPCs from DM patients. Anti-miR-130a inhibited whereas miR-130a overexpression promoted EPC function. miR-130a negatively regulated Runx3 (mRNA, protein and promoter activity) in EPCs. Knockdown of Runx3 expression enhanced EPC function. MiR-130a also upregulated protein expression of ERK/VEGF and Akt in EPCs. In conclusion, miR-130a plays an important role in maintaining normal EPC function, and decreased miR-130a in EPCs from DM contributes to impaired EPC function, likely via its target Runx3 and through ERK/VEGF and Akt pathways.
    PLoS ONE 07/2013; 8(7):e68611. DOI:10.1371/journal.pone.0068611 · 3.23 Impact Factor
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    • "Another study using circulated EPCs from peripheral blood mononuclear cells was designed using the rabbit as a model. He et al. [89] demonstrated that after 4 weeks, transplantation of autologous EPCs enhanced endothelialisation and improved endothelial function of the denuded carotid artery. "
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    ABSTRACT: No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.
    04/2013; 2013:691830. DOI:10.1155/2013/691830
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