Implantation of BM cells transfected with phVEGF165 enhances functional improvement of the infarcted heart

Xu, Hongxin; Li, G.-S.; Jiang, Hong; Wang, J.; Lu, Jingxiao; Jiang, Wenyang; Qian, Huijun; Jiang, Xuejun; Li, X.-Y.; Li, J.-J.; Liu, W.-H.

doi:10.1080/14653240410006013

Cited by 13 publications

(9 citation statements)

References 22 publications

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“…Tang et al have reported that implantation of mesenchymal stem cells significantly elevated VEGF expression which was accompanied by increased vascular density and regional blood flow in the infarct zone [28]. Moreover, it has been reported that implantation of bone marrow stem cells transfected with phVEGF165 can increase the survival of implanted cells, and enhance the cardiac function after acute myocardial infarction [29]. The latter study also showed that VEGF protected cells against apoptosis.…”

Section: Bmscs Protected Cultured Cardiomyocytes Via Secretion Of Vegfmentioning

confidence: 48%

HIF-1α induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia

Dai

Wang

et al. 2007

Journal of Molecular and Cellular Cardiology

146

101

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Hypoxia inducible factor-1α (HIF-1α) is a proangiogenic transcription factor stabilized and activated under hypoxia. It regulates the expression of numerous target genes, including vascular endothelial growth factor (VEGF) and other cytoprotective proteins. In this study, we hypothesized that bone marrow stem cells (BMSCs) secrete growth factors which protect cardiomyocytes via HIF-1α pathway.Methods-BMSCs were obtained from transgenic mice overexpressing green fluorescent protein (GFP). The study was carried out in vitro using co-culture of BMSCs with cardiomyocytes. LDH release, MTT uptake, DNA fragmentation and annexin-V positive cells were used as cell injury markers. The level of HIF-1α protein as well as its activated form and VEGF were measured by ELISA. The expression of HIF-1α and VEGF in BMSCs were analyzed by quantitative PCR and cellular localization was determined by immunohistochemistry.Results-LDH release was increased and MTT uptake was decreased after exposure of cardiomyocytes to hypoxia for 24 hours, which were prevented by co-culturing cardiomyocytes with BMSCs. Cardiomyocyte apoptosis induced by hypoxia and H 2 O 2 was also reduced by co-culture with BMSCs. VEGF release from BMSCs was significantly increased in parallel with high level of HIF-1α in BMSCs following anoxia or hypoxia in time-dependent manner. Although no significant up-regulation could be seen in HIF-1α mRNA, HIF-1α protein and its activated form were markedly increased and translocated to the nucleus or peri-nuclear area. The increase and translocation of HIF-1α in BMSCs were completely blocked by 2-methoxyestradiol (2-ME2; 5μmol), a HIF-1α inhibitor. Moreover, the protection of cardiomyocytes by BMSC and VEGF secretion were abolished by neutralizing HIF-1α antibodies in a concentration dependent manner (200~ 3200ng/ml).Conclusion-Bone marrow stem cells protect cardiomyocytes by up-regulation of VEGF via activating HIF-1α.

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Section: Bmscs Protected Cultured Cardiomyocytes Via Secretion Of Vegfmentioning

confidence: 48%

HIF-1α induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia

Dai

Wang

et al. 2007

Journal of Molecular and Cellular Cardiology

146

101

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“…BrdU-positive cells also incorporated in the structure of large vessels and colocalized with endothelial and smooth muscle [19,[26][27][28][29]. Increase in blood supply in infarcted area, as a result of neovascularization, would prevent further necrosis or apoptosis of hypertrophied but otherwise viable myocardium, and increase viability of implanted cells, thus improving ventricular function [30,31]. Bittira et al reported that pretreatment of marrow stromal stem cell with 5-aza-2¢ deoxycytidine, which is an active metabolite of 5-azacytidine, had better phenotypic outcome compared with untreated stromal cells when they were injected directly into the scar created by cryoinjury [32].…”

Section: Discussionmentioning

confidence: 97%

The similar effect of transplantation of marrow-derived mesenchymal stem cells with or without prior differentiation induction in experimental myocardial infarction

et al. 2007

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Marrow-derived mesenchymal stem cells (MSCs) have been heralded as a source of great promise for the regeneration of the infarcted heart. There is no clear data indicating whether or not in vitro differentiation of MSCs into major myocardial cells can increase the beneficial effects of MSCs. The aim of this study is to address this issue. To induce MSCs to transdifferentiate into cardiomyocyte-like and endothelial-like cells, 5-azacytidine and vascular endothelial growth factor (VEGF) were used, respectively. Myocardial infarction in rabbits was generated by ligating the left anterior descending coronary artery. Animals were divided into three experimental groups: I, control group; II, undifferentiated mesenchymal stem cell transplantation group; III, differentiated mesenchymal stem cell transplantation group; which respectively received peri-infarct injections of culture media, autologous undifferentiated MSCs and autologous differentiated MSCs. General pathology, immunohistochemistry, electron microscopy and echocardiography were performed in order to search for myocardial regeneration and improvement of cardiac function. In Groups II and III, implanted cells transdifferentiate into myocardial cells within 28 days post injection in a similar manner, and well-developed ultra structures formed within transplanted cells. Improvements in left ventricular function and reductions in infarcted area were observed in both cell-transplanted groups to the same degree. Vascular density was similar in Groups II and III and significantly higher in these groups compared with the control group. There is no need for prior differentiation induction of marrow-derived MSCs before transplantation and peri-infarct implantation of MSCs can efficiently regenerate the infarcted myocardium and improve cardiac function.

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“…We have read with interest the original research article by Xu et al [1] entitled 'Implantation of BM cells transfected with phVEGF 165 enhances functional improvement of the infracted heart'. The authors have successfully demonstrated transfection of the BM mononuclear cell (BM-MNC) fraction with phVEGF 165 (plasmid human vascular endothelial growth factor) to achieve /65% transfection efficiency, which is quite high considering the fact that it was mediated through a non-viral vector.…”

Section: Hkh Haider and M Ashrafmentioning

confidence: 97%

Implantation of genetically manipulated BM cells for cardiac repair

Haider

Ashraf

2005

Cytotherapy

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Implantation of BM cells transfected with phVEGF165 enhances functional improvement of the infarcted heart

Cited by 13 publications

References 22 publications

HIF-1α induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia

HIF-1α induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia

The similar effect of transplantation of marrow-derived mesenchymal stem cells with or without prior differentiation induction in experimental myocardial infarction

Implantation of genetically manipulated BM cells for cardiac repair

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