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Therapeutic benefit of bone marrow-derived endothelial progenitor cell transplantation after experimental aneurysm embolization with coil in rats.

ABSTRACT: Aneurysm embolization with coil is now widely used clinically. However, the recurrence of aneurysms after embolization has always plagued neurosurgeons because the endothelial layer of the aneurysm neck loses its integrity after being embolized by coil. Bone marrow-derived endothelial progenitor cells (BM-EPCs) could be incorporated into injured endothelium and differentiate into mature endothelial cells during vascular repairing processes. The aim of our study is to explore the effects of BM-EPCs on aneurysm repairing and remodeling in a rat embolization model of abdominal aortic aneurysm. BM-EPC proliferation, migration and tube formation were not affected by super-paramagnetic iron oxide nanoparticle (SPIO) labeling compared to the controls (p>0.05). The number of SPIO-labeled cells greatly increased in EPC transplanted rats compared to that of phosphate buffered saline treated rats. SPIO-labeled EPC (SPIO-EPC) are mainly located in the aneurysm neck and surrounded by fibrous tissue. A histology study showed that the aneurysm orifice was closed with neointima and the aneurysm was filled with newly formed fibrous tissue. The SPIO-EPC accumulated in the aneurysm neck, which accelerated focal fibrous tissue remodeling, suggesting that BM-EPCs play a crucial role in repairing and remodeling the aneurysm neck orifice.

SUBMITTER: Zhang S

PROVIDER: S-EPMC3938595 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Therapeutic benefit of bone marrow-derived endothelial progenitor cell transplantation after experimental aneurysm embolization with coil in rats.

Zhang Song S An Qingzhu Q Li Qianyun Q Huang Jun J Chen Xi X Chen Xiaoyan X Zhang Jun J Wang Yongting Y Yang Guo-Yuan GY Zhu Wei W

PloS one 20140228 2

Aneurysm embolization with coil is now widely used clinically. However, the recurrence of aneurysms after embolization has always plagued neurosurgeons because the endothelial layer of the aneurysm neck loses its integrity after being embolized by coil. Bone marrow-derived endothelial progenitor cells (BM-EPCs) could be incorporated into injured endothelium and differentiate into mature endothelial cells during vascular repairing processes. The aim of our study is to explore the effects of BM-EP ...[more]

PMID: 24587209

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Project description:Unlabelled: This study explored a new approach to enhance aneurysm (AN) neck endothelialization via erythropoietin (EPO)-induced endothelial progenitor cell (EPC) stimulation. Results suggest that EPO enhanced the endothelialization of a coiled embolization AN neck by stimulating EPCs via vascular endothelial growth factor modulation. Thus, the promotion of endothelialization with EPO provides an additional therapeutic option for preventing the recurrence of ANs. Endovascular coil embolization is an attractive therapy for cerebral ANs, but recurrence is a main problem affecting long-term outcomes. In this study, we explored a new approach to enhance AN neck endothelialization via EPO-induced EPC stimulation. Ninety adult male Sprague-Dawley rats were selected for an in vivo assay, and 60 of them underwent microsurgery to create a coiled embolization AN model. The animals were treated with EPO, and endothelial repair was assessed via flow cytometry, immunofluorescence, electronic microscopy, cytokine detection, and routine blood work. EPO improved the viability, migration, cytokine modulation, and gene expression of bone marrow-derived EPCs and the results showed that EPO increased the number of circulating EPCs and improved endothelialization compared with untreated rats (p < .05). EPO had no significant effect on the routine blood work parameters. In addition, the immunofluorescence analysis showed that the number of KDR(+) cells in the AN neck was elevated in the EPO-treated group (p < .05). Further study demonstrated that EPO promoted EPC viability and migration in vitro. The effects of EPO may be attributed to the modulation of vascular endothelial growth factor (VEGF). In particular, EPO enhanced the endothelialization of a coiled embolization AN neck by stimulating EPCs via VEGF modulation. Thus, the promotion of endothelialization with EPO provides an additional therapeutic option for preventing the recurrence of ANs.SignificanceErythropoietin (EPO) is involved in erythropoiesis and related conditions and is reported to enhance stem-cell mobilization from bone marrow while elevating stem-cell viability and function. In this study, EPO was also found to stimulate endothelial progenitor cells to induce the endothelialization of a coiled embolic aneurysm neck via vascular endothelial growth factor modulation. Endothelialization induction provides an additional therapeutic opportunity during vascular inner layer repair and remodeling. The results provide important information on the unique role EPO plays during vascular repair and remodeling.

Project description:ObjectivePrevious reports have revealed a high incidence of type II endoleak (T2EL) after endovascular aneurysm repair (EVAR). The incidence of T2EL after EVAR is reduced by pre-emptive embolization of aneurysm sac side branches (ASSB) and aneurysm sac coil embolization (ASCE). This study aimed to investigate whether different preventive interventions for T2EL were correlated with suppression of aneurysm sac expansion and reduction of the re-intervention rate.MethodsThe PubMed, Web of Science, MEDLINE and Embase databases, and conference proceedings were searched to identify articles on EVAR with or without embolization. The study was developed in line with the Participants, Interventions, Comparisons, Outcomes, and Study design principles and was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We used network meta-analysis based on multivariate random-effects meta-analysis to indirectly compare outcomes of different strategies for embolization during EVAR.ResultsA total of 31 studies met all inclusion criteria and were included in the qualitative and quantitative syntheses. The included studies were published between 2001 and 2022 and analyzed a total of 18,542 patients, including 1,882 patients who received prophylactic embolization treatment during EVAR (experimental group) and 16,660 who did not receive prophylactic embolization during EVAR (control group). The effect of pre-emptive embolization of the inferior mesenteric artery (IMA) (IMA-ASSB) in preventing T2EL was similar (relative risk [RR] 1.01, 95% confidence interval [CI] 0.38-2.63) to the effects of non-selective embolization of ASSB (NS-ASSB) and ASCE (RR 0.88, 95% CI 0.40-1.96). IMA-ASSB showed a better clinical effect in suppressing the aneurysm sac expansion (RR 0.27, 95% CI 0.09-2.25 compared with NS-ASSB; RR 0.93, 95% CI 0.16-5.56 compared with ASCE) and reducing the re-intervention rate (RR 0.34, 95% CI 0.08-1.53 compared with NS-ASSB; RR 0.66, 95% CI 0.19-2.22 compared with ASCE). All prophylactic embolization strategies improved the clinical outcomes of EVAR.ConclusionProphylactic embolization during EVAR effectively prevents T2EL, suppresses the aneurysm sac expansion, and reduces the re-intervention rate. IMA embolization demonstrated benefits in achieving long-term aneurysm sac stability and lowering the risk of secondary surgery. NS-ASSB more effectively reduces the incidence of T2EL, while IMA embolization alone or in combination with ASCE enhances the clinical benefits of EVAR. In addition, as network meta-analysis is still an indirect method based on a refinement of existing data, more studies and evidence are still needed in the future to establish more credible conclusions.

Dataset Information

Therapeutic benefit of bone marrow-derived endothelial progenitor cell transplantation after experimental aneurysm embolization with coil in rats.

Publications

Therapeutic benefit of bone marrow-derived endothelial progenitor cell transplantation after experimental aneurysm embolization with coil in rats.

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