Transplantation of human umbilical cord-derived endothelial progenitor cells promotes re-endothelialization of the injured carotid artery after balloon injury in New Zealand white rabbits / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cell transplantation has great potential for promoting endothelial repair and reducing the complications of percutaneous coronary intervention (PCI). The aim of this study was to investigate the effect of transplantation of human umbilical cord blood endothelial progenitor cells (EPCs) on injured arteries.</p><p><b>METHODS</b>Umbilical cord blood mononuclear cells were obtained from post-partum lying-in women, and EPCs were isolated, cultured, expanded and identified by immunofluorescence. The carotid arterial endothelium of New Zealand white rabbits was injured by dilatation with a 3F balloon, and the EPCs were injected into the lumen of the injured artery in the transplanted group (n = 16), while an equal volume of phosphated buffered saline (PBS) was injected into the control group after balloon injury (n = 16). The animals were sacrificed after either 2 or 4 weeks, and the grafted cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibodies. Arterial cross sections were analyzed by pathology, immunohistochemistry and morphometry to evaluate the reparative effects of EPCs. Proliferating cell nuclear antigen (PCNA) and transforming growth factor (TGF)-β1 mRNA expression were detected by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Fluorescence-labeled EPCs were found in the neointima. The neointimal area and the neointimal/medial area ratio were significantly lower in the transplanted group than in the control group (P < 0.05). von Willebrand factor (vWF) immunohistostaining showed more VWF-positive cells in the transplanted animals than in the controls (8.75 ± 2.92 vs. 4.50 ± 1.77, P < 0.05). Compared with the control group, the transplanted group had lower expression of PCNA mRNA (0.67 ± 0.11 vs. 1.25 ± 0.40, P < 0.01) and higher expression of TGF-β1 mRNA (1.10 ± 0.21 vs. 0.82 ± 0.07, P < 0.05).</p><p><b>CONCLUSIONS</b>EPCs derived from human umbilical cord blood were successfully transplanted into injured vessels. The transplanted EPCs inhibited neointimal hyperplasia and promoted vascular re-endothelialization.</p>

Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cell-based vascular therapies of endothelial progenitor cells (EPCs) mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs (hUCB-EPCs) in rat with acute myocardial infarction.</p><p><b>METHODS</b>Human umbilical cord blood (hUCB) mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and fluorescein isothiocyanate-conjugated Ulex europaeus lectin (FITC-UEA-l). The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density (CAD) was evaluated by anti-VIII immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibody, representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen (PCNA), platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor (VEGF) were detected to investigate the underlying mechanisms of cell differentiation and revascularization.</p><p><b>RESULTS</b>The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VIII staining demonstrated a higher degree of microvessel formation in EPCs transplanted rats, associated with a significant improvement of global heart function in terms of the increase of left ventricular end-systolic pressure (LVESP), +dp/dtmax and -dp/dtmax as well as the decrease of LVEDP in rats with EPCs therapy comparing to the control rats (P < 0.05). Moreover, the expression of the rat PCNA mRNA and PECAM were both enhanced in the EPCs group compared with that of the control group.</p><p><b>CONCLUSIONS</b>The human umbilical cord blood-derived EPCs could incorporate into new-born capillaries in rat myocardium, induce revascularization and improve the proliferation activity in the peri-infarct area, resulting in the improvement of global heart function. This may indicate a promising stem cell resource in cell-based therapy for ischaemic diseases.</p>

Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human umbilical cord blood contains an abundance of immature stem/progenitor cells, which may participate in the repair of hearts that have been damaged by myocardial infarction (MI). This study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation on cardiac function and left ventricular remodeling in rat model of MI.</p><p><b>METHODS</b>Forty-five male Wistar rats were randomized into three groups: MI or control group (n = 15), MI plus cell transplantation (n = 15), and sham group (n = 15). Acute myocardial infarction (AMI) was established by ligating the left anterior descending artery, thereafter, hUCBC were implanted into the marginal area of infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC following the same protocol. Left ventricular function assessment was carried out by echocardiography and invasive hemodynamic measurements one month post MI. All rats were sacrificed for histological and immunochemical examinations.</p><p><b>RESULTS</b>The transplanted hUCBC survived and engaged in the process of myocardial repair in the host heart. Echocardiography demonstrated that left ventricular function improved significantly in the rats that underwent cell transplantation. Hemodynamic studies found a significantly decreased left ventricular end-diastolic pressure (LVEDP) [(21.08 +/- 8.10) mmHg vs (30.82 +/- 9.59) mmHg, P < 0.05], increase in +dp/dt(max) [(4.29 +/- 1.27) mmHg/ms vs (3.24 +/- 0.75) mmHg/ms, P < 0.05), and increase in -dp/dt(max) [(3.71 +/- 0.79) mmHg/ms vs (3.00 +/- 0.49) mmHg/ms, P < 0.05] among MI group with hUCBC transplantation when compared with MI/control group. Masson's trichrome staining revealed that the collagen density in the left ventricle was significantly lower in rats of transplantation group than that in the MI control groups [(6.33 +/- 2.69)% vs (11.10 +/- 3.75)%, P < 0.01]. Based on immunostaining of alpha-actin, the numbers of microvessels were significantly (P < 0.01) increased at the boundary of infarction site. Similarly higher mRNA expression of vascular endothelial growth factor (VEGF) 164 and VEGF188 were found at 7- and 28-day post cell transplantation in MI group with hUCBC transplantation when compared with MI/control group.</p><p><b>CONCLUSIONS</b>Transplanted hUCBC can survive in host myocardium without immunorejection, significantly improve left ventricular remodeling after AMI and promote a higher level of angiogenesis in the infarct zones. All these factors beneficially affect cardiac repair in the setting of MI. Therefore human umbilical cord blood may be potential source for cell-based therapy for AMI.</p>

Beneficial effects of human umbilical cord blood mononuclear cells transplantation on rats with experimental myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>Human umbilical cord blood contains abundant immature stem/progenitor cells, which may contribute to the repair of infarcted myocardium. Present study aimed to explore the feasibility and effects of human umbilical cord blood mononuclear cells (HUCBC) transplantation for the treatment of myocardial infarction.</p><p><b>METHODS</b>Forty-five male Wistar rats were randomly divided into three groups: (1) Myocardial infarction (MI plus vehicle, n = 15), (2) MI plus cell transplantation (HUCBC were implanted into the peri-infarct area immediately after MI, n = 15), (3) Normal control group (n = 15). After echocardiography and hemodynamic measurements, the rats were sacrificed for histological and immunochemical examinations one month post MI.</p><p><b>RESULTS</b>The transplanted HUCBC survived and participated the repair process in host heart. Significantly improved left ventricular function was evidenced by echocardiography in cell transplantation group compared to the MI control group. Left ventricular end-diastolic pressure was significantly reduced LVEDP (21.08 +/- 8.10) vs (30.82 +/- 9.59) mm Hg, P < 0.05], +dp/dt(max) [(4.29 +/- 1.27) vs (3.24 +/- 0.75) mm Hg/ms, P < 0.05] and -dp/dt(max) increased [(3.71 +/- 0.79) vs (3.00 +/- 0.49) mm Hg/ms, P < 0.05] in cell transplantation rats compared with MI control rats. vWF immunostaining examination showed significantly increased microvessels within the boundary of infarcted myocardium in cell transplantation group compared to the MI control group (P < 0.01).</p><p><b>CONCLUSIONS</b>HUCBC transplantation may improve cardiac function in MI rats by promoting microvessel formation.</p>

Efficacy and restenosis of cypher stent in elderly patients with coronary heart disease / 中华老年医学杂志

Objective To investigate the efficacy and security of cypher stent(sirolimus-eluting stent)in the treatment of old patients with coronary heart disease(CHD).Methods From November 2002 to May 2005,328 elderly CHD cases(age:60-86 years)were treated with 415 Cypher stents.Among the 328 patients,66 had ST-segment elevation of myocardial infarction,21 had non ST-segment elevation of myocardial infarction,149 had unstable angina and 92 had stable angina.As for lesion characteristics,diffuse disease was found in 91 case(26.1%),bifurcation lesions in 68 cases(19.6%),chronic total occlusion lesions in 56 cases(16.0%),in-stent restenosis in 14 cases and ostial lesions in 15 case.The immediate angiographic outcome,major cardiac event(MACE) and angiographic follow-up at 6 months were assessed.Results Stent implantation was successfully achieved in 99% patients with CHD.Acute and sub-acute stent thrombosis occurred in 2 patients,late stent thrombosis with AMI occurred in 2 patients,1 died during the 6 months follow-up.The MACE rate during hospitalization was 0.6% and 3.6% during 6 months follow-up.Angiographic follow-up in 84 patients at 6 months showed that in-stent restenosis rate(ISR)was 8.3%(restenosis within the stents was 2.4%).The target vessel revascularization(TLR)rate was 5.9%.Conclusions Cypher stent implantation in CHD is safe and effective,the ISR rate and TLR rate are significantly lower than those of bare metal stents.