Therapeutic Benefit of Bone Marrow–Derived Endothelial Progenitor Cell Transplantation after Experimental Aneurysm Embolization with Coil in Rats

Zhang, Song; An, Qingzhu; Li, Qianyun; Huang, Jun; Chen, Xi; Chen, Xiaoyan; Zhang, Jun; Wang, Yongting; Yang, Guo‐Yuan; Zhu, Wei

doi:10.1371/journal.pone.0090069

Cited by 14 publications

(15 citation statements)

References 28 publications

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“…Our previous study demonstrated the effect of bone marrow-derived EPCs in aneurysm neck endothelialization. 30 In the present study, we further demonstrated that the numbers of circulating EPCs increased in the rosuvastatin-treated rats, and more KDR+ cells adhered to the endothelial layer in the aneurysm neck (Fig. 3), indicating that rosuvastatin could promote EPC attachment to the aneurysm neck.…”

Section: Discussionsupporting

confidence: 74%

“…1 In addition, we have previously shown that bone marrow-derived EPCs play a crucial role in the closure and reconstruction of the aneurysm neck after coil embolization. 30 EPCs have demonstrated a robust effect on aneurysm neck endothelialization and the prevention of recurrence. Because EPCs are involved in the vascular repair and remodeling process, EPC-mediated therapy has been proposed as a potential treatment for vascular disease.…”

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confidence: 99%

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Rosuvastatin for enhancement of aneurysm neck endothelialization after coil embolization: promotion of endothelial progenitor cells in a rodent model

Liu

Chen

et al. 2016

JNS

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OBJECT Coil embolization is a safe, efficient, and minimally invasive technique for the treatment of intracranial aneurysms. However, coil embolization is associated with a higher risk of recurrence than clip ligation. In this study, the authors explore a new approach through the promotion of endothelial progenitor cells (EPCs) to optimize endothelialization of the aneurysm neck and reduce the risk of recurrence. METHODS A coiled aneurysm model was created in 48 adult male Sprague-Dawley rats via microsurgery. Half of these animals were treated with rosuvastatin (20 mg/kg) in saline via gavage for 10, 20, or 30 days. The other half were administered saline without rosuvastatin. An additional 15 rats underwent “mock surgery” (identical anesthesia and saline gavage but no surgery). The endothelial repair process in the coiled aneurysms was evaluated via flow cytometry, im-munostaining, and electronic microscopy. The mock surgery group was used for comparison in flow cytometry studies. The effects of rosuvastatin on viability and functioning of Sprague-Dawley rat bone marrow-derived EPCs were also explored via MTT, migration, and tube formation assays. RESULTS The aneurysm neck repair score was significantly higher in the rosuvastatin-treated rats than in the untreated rats (p < 0.05). The circulating EPC count was increased and maintained at a higher level in rosuvastatin-treated rats compared with the aneurysm rats that did not receive rosuvastatin (p < 0.05). Immunostaining showed that the aneurysm neck endothelium was more integrated and the number of kinase insert domain receptor-positive cells was increased in the rosuvastatin-treated rats. Further study demonstrated that rosuvastatin promoted EPC proliferation, migration, and tube formation. CONCLUSIONS Rosuvastatin promoted endothelialization of the coiled aneurysm neck via induction of EPCs, suggesting that promoting endothelialization provides an additional therapeutic opportunity during vascular endothelium repair.

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Section: Discussionsupporting

confidence: 74%

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confidence: 99%

Rosuvastatin for enhancement of aneurysm neck endothelialization after coil embolization: promotion of endothelial progenitor cells in a rodent model

Liu

Chen

et al. 2016

JNS

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“…In this study, bone marrow derived endothelial progenitor cells were labeled and transfused following aneurysm embolization. Zhang et al demonstrated that the labeled cells accumulated at the aneurysm neck accelerating repair and remodeling of the neck 63 .…”

Section: Application Of Biological Findingsmentioning

confidence: 99%

Mechanisms of Healing in Coiled Intracranial Aneurysms: A Review of the Literature

Brinjikji

Kallmes

Kadirvel

2014

American Journal of Neuroradiology

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Summary Recanalization of intracranial aneurysms following endovascular coiling remains a frustratingly common occurrence. An understanding of the molecular and histopathological mechanisms of aneurysm healing following coil embolization is essential to improving aneurysm occlusion rates. Histolopathologic studies in coiled human and experimental aneurysms suggest that during the first month post-coiling, thrombus formation and active inflammation occur within the aneurysm dome. Several months following embolization, the aneurysm is excluded from the parent vessel by formation of a neointimal layer, which is often thin and discontinuous, across the aneurysm neck. Numerous coil modifications and systemic therapies have been tested in animals and humans in an attempt to improve the aneurysm healing process; these modifications have met with variable levels of success. In this review, we summarize the histopathologic and molecular biology of aneurysm healing and discuss how these findings have been applied in an attempt to improve angiographic outcomes in patients harboring intracranial aneurysm.

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“…There is a growing interest in using circulating EPCs in clinical trials for ischemia, stroke, and vascular injury [24][25][26][27]. Our previous study [16] also showed that bone marrow-derived EPCs play a crucial role in the closure and reconstruction of the aneurysm neck orifice after aneurysm coiling.…”

Section: Discussionmentioning

confidence: 89%

“…Adult Sprague-Dawley rats (150-200 g) were used in the experiments (Slac Laboratory Animal, Shanghai, China, http://english.sibs.cas.cn/rs/fs/shanghailaboratoryanimalcentercas). The coiled AN model was prepared as previously reported [16]. The AN-EPO group was administered 1.5 mg/kg Recombinant Rat EPO (R&D Systems, Minneapolis, MN, https://www.rndsystems.com) injected subcutaneously, and the AN group was given an equal amount of saline subcutaneously.…”

Section: Methodsmentioning

confidence: 99%

Erythropoietin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in an Aneurysm Neck After Coil Embolization by Modulating Vascular Endothelial Growth Factor

Liu

Zhou

et al. 2016

Stem Cells Translational Medicine

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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 EPOinduced 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. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1182-1189 SIGNIFICANCE Erythropoietin (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.

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Therapeutic Benefit of Bone Marrow–Derived Endothelial Progenitor Cell Transplantation after Experimental Aneurysm Embolization with Coil in Rats

Cited by 14 publications

References 28 publications

Rosuvastatin for enhancement of aneurysm neck endothelialization after coil embolization: promotion of endothelial progenitor cells in a rodent model

Rosuvastatin for enhancement of aneurysm neck endothelialization after coil embolization: promotion of endothelial progenitor cells in a rodent model

Mechanisms of Healing in Coiled Intracranial Aneurysms: A Review of the Literature

Erythropoietin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in an Aneurysm Neck After Coil Embolization by Modulating Vascular Endothelial Growth Factor

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