Transplantation Of Endothelial Cells Research Articles

Intramyocardial transplantation of endothelial progenitor cells and erythropoietin: a new scope for the treatment of cardiovascular disease

Intramyocardial transplantation of endothelial progenitor cells and erythropoietin: a new scope for the treatment of cardiovascular disease

Endothelial Progenitor Cells Promote Astrogliosis following Spinal Cord Injury through Jagged1-Dependent Notch Signaling

Interactions between endothelial and neural stem cells are believed to play a critical role in the kinetics of neural stem cells in the central nervous system. Here we demonstrate that endothelial progenitor cells promote the repair of injured spinal cord through the induction of Notch-dependent astrogliosis and vascular regulation. The transplantation of Jagged1(+/+) endothelial progenitor cells, but not Jagged1(-/-) endothelial progenitor cells, increased the number of reactive astrocytes during the acute phase, and improved functional recovery following spinal cord injury. Expression of the Notch effector Hes5 was upregulated in the injured spinal cord after Jagged1(+/+) endothelial progenitor cell transplantation. Furthermore, we found that the Notch ligand Delta-like-1 was highly expressed in Jagged1(-/-) endothelial progenitor cells. Transplantation of Delta-like-1, as well as Jagged1-overexpressing 3T3 cells, revealed that only Jagged1-overexpressing 3T3 stromal cells enhanced astrogliosis following spinal cord injury. In addition, Jagged1(+/+) endothelial progenitor cells exhibited not only dramatic pro-angiogenic effects, but also morphologically abnormal vessel stabilization, compared with Jagged1(-/-)endothelial progenitor cells in injured spinal cord. Thus, transplanted endothelial progenitor cells promote astrogliosis, vascular regulation, and spinal cord regeneration through activation of Jagged1-Notch signaling.

In vitro labeling of endothelial progenitor cells isolated from peripheral blood with superparamagnetic iron oxide nanoparticles.

The transplantation of endothelial progenitor cells (EPCs) provides a novel method for the treatment of human tumors or vascular diseases. Magnetic resonance imaging (MRI) has proven to be effective in tracking transplanted stem cells by labeling the cells with superparamagnetic iron oxide (SPIO) nanoparticles. The SPIO has been used to label and track the EPCs; however, the effect of SPIO upon EPCs remains unclear on a cellular level. In the present study, EPCs were labeled with home-synthesized SPIO nanoparticles in vitro and the biological characteristics of the labeled EPCs were evaluated. The EPCs were isolated from the peripheral blood of New Zealand rabbits and cultured in fibronectin-coated culture flasks. The EPCs were labeled with home-synthesized SPIO nanoparticles at a final iron concentration of 20 μg/ml. Labeled EPCs were confirmed with transmission electron microscopy and Prussian blue staining. The quantity of iron/cell was detected by atomic absorption spectrometry. The membranous antigens of EPCs were detected by cytofluorimetric analysis. Cell viability and proliferative capability between the labeled and unlabeled EPCs were compared. The rabbit EPCs were effectively labeled and the labeling efficiency was approximately 95%. The SPIO nanoparticles were localized in the endosomal vesicles of the EPCs, which were confirmed by transmission electron microscopy. No significant differences were found in cell viability and proliferative capability between labeled and unlabeled EPCs (P>0.05). In conclusion, rabbit peripheral blood EPCs were effectively labeled by home-synthesized SPIO nanoparticles, without influencing their main biological characteristics.

Fibrin Promotes Survival and Differentiation of Endothelial Progenitor Cells after Transplantation

Transplantation of endothelial progenitor cells (EPCs) is a potential therapy for angiogenesis and improving microcirculation of the local tissue in ischemic diseases. However, survival and differentiation of the transplanted EPCs decrease so that efficiency of EPC transplantation is undesirable. This investigation was designed to investigate cytoprotective effects of fibrin in ischemic microenvironment. VEGFR‐2+ cells were sorted from mononuclear cells in bone marrow of male SD rats. Fibrin glue was prepared by mixing fibrinogen and thrombin. The cells were seeded in fibrin or fibrin supplemented with VEGF. The cells in fibrin glue may migrate well. Under hypoxia and withdraw of serum and glucose, apoptotic and necrotic cells in fibrin group were less than that in control group. After incubation in fibrin glue for two weeks, the cells differentiated into endothelial cells and organized into capillary‐like structures. After transplantation of fibrin‐delivered cells into the infracted myocardium of female rats, angiogenesis and cardiac regeneration increased, cardiac functions were improved significantly. These results demonstrate that fibrin has protective effects for survival and differentiation of EPCs. Delivery with fibrin in EPC transplantation is effective for repairing the infracted myocardium.

Spin-Labeling Magnetic Resonance Imaging Detects Increased Myocardial Blood Flow After Endothelial Cell Transplantation in the Infarcted Heart

We quantified absolute myocardial blood flow (MBF) using a spin-labeling MRI (SL-MRI) method after transplantation of endothelial cells (ECs) into the infarcted heart. Our aims were to study the temporal changes in MBF in response to EC transplantation and to compare regional MBF with contractile function (wall motion) and microvascular density. We first validated the SL-MRI method with the standard microsphere technique in normal rats. We then induced myocardial infarction in athymic rats and injected 5 million ECs (human umbilical vein endothelial cells) suspended in Matrigel or Matrigel alone (vehicle) along the border of the blanched infarcted area. At 2 weeks after myocardial infarction, MBF averaged over the entire slice (P=0.038) and in the infarcted region (P=0.0086) was significantly higher in EC versus vehicle group; the greater MBF was accompanied by an increase of microvasculature density in the infarcted region (P=0.0105 versus vehicle). At 4 weeks after myocardial infarction, MBF in the remote region was significantly elevated in EC-treated hearts (P=0.0277); this was accompanied by increased wall motion in this region assessed by circumferential strains (P=0.0075). Intraclass correlation coefficients and Bland-Altman plot revealed a good reproducibility of the SL-MRI method. MBF in free-breathing rats measured by SL-MRI is validated by the standard color microsphere technique. SL-MRI allows quantification of temporal changes of regional MBF in response to EC treatment. The proof-of-principle study indicates that MBF is a unique and sensitive index to evaluate EC-mediated therapy for the infarcted heart.

Abstract 2: IL-10 Modulates Mobilization of Bone Marrow Endothelial Progenitor Cells and Enhances Their Survival and Angiogenic Properties in Ischemic Myocardium

Endothelial progenitor cells (EPC) transplantation has been shown to enhance neovascularization and improve myocardial infarction (MI)-induced ventricular dysfunctions. However, persistent inflammation in the ischemic myocardium, adversely affect EPC survival and function, thereby compromising full benefits of EPC-mediated vascular repair. We hypothesized that modulation of IL-10 signaling in EPCs enhances their mobilization, survival and function in ischemic myocardium after MI. GFP-labeled EPC were transplanted intramyocardially after induction of MI, and the mice were treated with either saline or recombinant IL-10. EPC survival and EPC-mediated neovascularization and myocardial repair were evaluated. IL-10-treated mice showed increased number of GFP+EPCs retention that was associated with reduced EPC apoptosis in the myocardium (P<0.05). The engraftment of EPC into the vascular structures and the associated capillaries density was significantly higher in IL-10-treated mice (P<0.05). The above findings were corroborated with reduced infarct size, fibrosis and enhanced LV function (echocardiography) in IL-10+EPC group as compared to EPC+saline group. Invitro, IL-10-deficient EPCs showed higher LPS-induced apoptosis compared to WT-EPCs (P<0.05). IL-10 treatment induced VEGF expression in WT-EPCs which was abrogated by STAT3 inhibition (using curcurbitacin I). Furthermore, microRNA (miR) profile experiments identified significant increases in a number of pro-apoptotic and anti-angiogenic-related miRs in EPCs from IL-10 deficient mice. Interestingly, IL-10-deficient mice showed impaired MI-induced mobilization of bone marrow EPCs (Sca1+Flk1+ cells) into the circulation and the associated SDF-1 mRNA expression in the myocardium. Bone marrow transplantation studies involving replacement of IL-10-deficient marrow with WT marrow attenuated these effects. Invitro, LPS-induced CXCR4 expression was lower in IL-10-deficient EPCs as compared to WT-EPC. Taken together, our studies suggest that IL-10 enhances EPC mobilization, possibly in an SDF1-CXCR4 dependent manner and increased their survival and neovascularization and the associated myocardial repair, in part via activation of STAT3 signaling cascades.

Transplantation application and mechanisms of endothelial progenitor cells

Background Recent studies have demonstrated the importance of endothelial progenitor cells(EPCs)in maintaining normal endothelial function as well as endothelial repairing after vascular injury.Objective This review summarizes transplantation therapy of EPCs and discusses the mechanisms regulating the cells-mediated neovascularization and reendothelialization.Content The text describes the biological characteristics of EPCs,summarizes the application of endothelial progenitor cell transplantation and discusses potential mechanisms of EPCs.Trend Transplantation of EPCs can be a novel cellbased,endothelium-targeted therapeutic strategy for prevention and treatment of vascular disease and inflammation injury.The clinical application of EPCs still needs to be investigated deeply. Key words: Endothelial progenitor cell ; Transplantation ;

Effect of VEGF transfected endothelial progenitor cells transplantation in rat chronic ischemic myocardium

ObjectiveTo observe the effect of endothelial progenitor cells modified by VEGF transplanted in rat chronic ischemic myocardium.MethodRat bone marrow stem cells were isolated and induced into endothelial progenitor cells (EPCs)...

An experimental study on MR imaging of atherosclerotic plaque with SPIO marked endothelial cells in a rabbit model

To investigate how to label macrophages in atherosclerotic plaques with superparamagnetic iron oxide (SPIO) nanoparticles and trace SPIO with MR imaging. Atherosclerotic lesions of a rabbit model were induced by a combination of high-fat and high-cholesterol diet and subsequent endothelial abrasion of the abdominal aorta. SPIO particles were pretreated with poly-L-lysine. SPIO nanoparticles and SPIO-labeled human endothelial cells (ECV-304) were IV injected into model animals, respectively. The MRI scans and histopathological examination were performed 12 h and 24 h after the injection. The imaging and histopathological data were analyzed. Prussian blue staining of the vessel specimens indicated that SPIO particles were not found in the atheroma but in the Kupffer's cells of the liver after SPIO injection. However, the accumulation of SPIO particles in the atheroma was confirmed in animals received SPIO-labeled endothelial cell transplantation. The best quality MR scan sequences of rabbit abdominal aorta were T(2) WI fat suppression, T(1) WI, and DIR series, on which of MR image had a higher quality. Signal loss of the original incrassate plaque in the vessel wall on T(2) WI was found in 6 of 10 animals received SPIO-labeled endothelial cell transplantation. SPIO-labeled endothelial cells were superior to SPIO for MR imaging of atherosclerotic plaques.

604 Pre-clinical evaluation of biopolymer-delivered endothelial progenitor cells in hibernating myocardium

Hibernating myocardium is commonly observed in patients with severe diffuse coronary artery disease. Vasculogenic cell-based therapy, combined with tissue engineering, is a promising revascularization solution for patients who cannot benefit from established reperfusion therapies. However, there is a lack of large animal studies evaluating the advantages of endothelial progenitor cell (EPC) transplantation in combination with biopolymers. We sought to use a clinically relevant, large animal model of myocardial hibernation to examine the benefits of EPC and polymer therapy on myocardial perfusion, metabolism, and function.

Characterization of Chitosan-Hyaluronic Acid Blended Membranes and Their Effects on the Growth of Keratocytes

In order to construct a suitable scaffold for corneal cell culture and transplantation in vitro, various chitosan-hyaluronic acid blended membranes were prepared, and the properties of the blended membranes were studied. Rabbit keratocytes were seeded onto the blended membrane surfaces and the effects of the blended membranes on cell attachment and metabolism were investigated. The results showed that chitosan and hyaluronic acid (HA) were compatible in blended membranes. HA improved the homogeneity, crystallization and transparency, and decreased the tensile strength and hydrophilicity of blended membranes within the blending ratio of 1:0.05. Under the blending ratio of 1:0.02, HA reduced the harm that the chitosan membrane caused the cells and improved the biocompatibility between cells and membranes. Rabbit keratocytes grew and formed a confluent monolayer on the chitosan-hyaluronic acid blended membrane within a blending ratio of 1:0.02. All the results indicated that chitosan and HA were compatible within the blending ratio of 1:0.02, and the blended membranes had homogeneous structure, suitable physicochemical properties and biocompatibility with cells, this implied that the blended membranes could be used as a scaffold for corneal cell culture in vitro and as a potential carrier for corneal endothelial cell transplantation.

In vitro blood–brain barrier model adapted to repeated dose toxicological screening

Our previous study has demonstrated cultivation of bovine corneal endothelial cells (BCECs) on the chitosan–polycaprolactone (PCL) blends. BCECs could grow well and express physiological phenotypes after PCL was introduced into chitosan by means of blending. The feasibility of using chitosan–PCL-blended membranes as scaffold and carrier for corneal endothelial cell (CEC) transplantation is worthy of more investigation. In this work, we attempt to manufacture various blended membranes to bring BCEC cultivation into harmony by hybridizing two polymers with fine adjustment. Therefore, chitosan, which does not promote BCECs maturation, and PCL, which supports, BCEC proliferation, are combined to prepare the blends. Analyses of transmittance, proliferative, abilities, phenotypic expressions, extracellular matrix (ECM) protein production, and hemotoxylin and eosin (H&E) staining were executed step-by-step. From our observations, the blended membranes united respective characteristics. The cultured BCECs on the blends illustrated normal appearance and good proliferative abilities. Immunohistochemical staining verified physiologically phenotypic expressions of ZO-1 and Na-K ATPase. Western blot analysis also confirmed the existence of collagen type IV proteins. Furthermore, the formation of a continuous monolayer of cells attached on the blended membrane was confirmed by H&E staining. These results suggested that chitosan–PCL blended membranes may be an optimized biomaterial to fabricate bioengineered corneal endothelium and show potential to facilitate CEC transplantation in the future.

Graft survival and endothelial outcomes in the new era of endothelial keratoplasty

Corneal endothelial cells do not proliferative in vivo sufficiently to enable endothelial regeneration, and thus diseases of the corneal endothelium, which cause poor vision and discomfort, require treatment by transplantation of cadaveric donor corneal endothelial cells. The two major goals of any corneal transplant procedure are to restore vision and to promote longevity of the donor cornea by maintaining a healthy donor endothelial cell density. Over the last decade, the surgical treatment for endothelial disease has rapidly evolved toward endothelial keratoplasty, or selective tissue transplantation, and away from full-thickness penetrating keratoplasty (PK). While endothelial keratoplasty offers distinct advantages over PK in terms of visual outcomes and a smaller incision, the new surgical manipulations of the fragile donor tissue cause significant donor endothelial cell trauma. As a result, donor endothelial cell loss is much higher during the first month after Descemet stripping endothelial keratoplasty (DSEK) compared to after PK, and the primary (or more appropriately, iatrogenic) graft failure rate of 5% remains unacceptably high. Nevertheless, the rate of endothelial cell loss rapidly decreases beyond 6 months after DSEK, and thus endothelial cell loss at 5 years after DSEK appears to be lower than that at 5 years after PK. In the absence of primary (iatrogenic) graft failure, graft survival through 5 years after DSEK is similar to that after PK. Given the promising longer-term endothelial outcomes of DSEK, the quest for optimizing the visual outcomes has spurred interest in Descemet membrane endothelial keratoplasty (DMEK). While early results after DMEK suggest better visual outcomes than after DSEK, the technique needs to be simplified, and longer-term outcomes must show an advantage over DSEK with respect to vision, endothelial cell loss, and graft survival. DMEK also has a high rate of primary (iatrogenic) graft failure, and additional donor tissue wastage occurs when preparation of DMEK grafts is unsuccessful. This review discusses endothelial keratoplasty techniques and the associated endothelial outcomes.

Autotransplantation of circulating endothelial progenitor cells protects against lipopolysaccharide-induced acute lung injury in rabbit

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are leading causes of morbidity and mortality in critically ill patients. Recent studies suggest that endothelial progenitor cells (EPCs) transplantation could become a novel cell-based therapeutic strategy for ALI/ARDS, but the exact therapeutic effect and possible mechanisms still need to be elucidated. In the present study, autologous circulating EPCs were obtained from rabbits using Ficoll centrifugation and cultured in vitro for 7days. ALI was induced in rabbits by lipopolysaccharide (LPS), and EPCs were administered systemically. Fluorescence microscopy showed that CM-DiI labelled EPCs could migrate to the injured lung tissues. Reduced pulmonary edema level, inflammation, hemorrhage and hyaline membrane formation were present in rabbit treated with EPCs. EPCs autotransplantation significantly decreased the expression of adhesion molecules of sICAM-1 and P-selectin. Furthermore, EPCs administration mediated a down-regulation of proinflammatory responses (reducing IL-1β and TNF-α) while increasing the anti-inflammatory cytokine IL-10. Apoptosis of endothelial and epithelial cells was substantially reduced in EPCs-treated rabbit. Those findings suggest that autotransplantation of circulating EPCs can reduce the severity of LPS-induced ALI. Possible mechanisms include EPCs engraftment and reendothelization, down-regulation of adhesion molecules, alleviation of inflammatory response and apoptosis prevention.

Application of an Endothelialized Modular Construct for Islet Transplantation in Syngeneic and Allogeneic Immunosuppressed Rat Models

Modular tissue engineering is a novel approach to assemble tissues with an inherent vascularization. In this article, we evaluated whether endothelialized module-driven vascularization enhances islet engraftment in diabetic rats. Two thousand islets were transplanted in the omental pouch of syngeneic and allogeneic immunosuppressed diabetic recipients as free islets, islets in collagen modules, or islets in endothelialized modules. Transplantation of islets in endothelialized modules significantly increased the vessel density compared with controls. Donor green fluorescent protein-positive endothelial cells (ECs) formed vessels in proximity to transplanted islets; donor vessels connected to host vasculature as the vessels included erythrocytes in their lumens and were supported by host smooth muscle cells by 21 days. Transplantation of 2000 islets reversed diabetes in two of five of syngeneic recipients until 60 days, although there was no apparent benefit to islet function of adding ECs relative to collagen modules without EC. However, there was a trend toward increased viability when islets were implanted in endothelialized modules compared with collagen modules at 21 days. Meanwhile, 2000 islets in allogeneic immunosuppressed recipients lowered blood glucose levels short term, but there was graft failure within 1 week. This study explored the simultaneous transplantation of primary ECs with islets in diabetic recipients. The endothelialized modular approach increased vessel density around transplanted islets. Further modulation (i.e., acceleration) of vessel maturation, is presumed necessary to improve islet engraftment.

Beneficial Effect of Autologous Transplantation of Endothelial Progenitor Cells on Steroid-Induced Femoral Head Osteonecrosis in Rabbits

Femoral head osteonecrosis (ON) is a serious complication of steroid administration. We examined whether implantation of autologous bone marrow-derived endothelial progenitor cells (EPCs) can augment neovascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. Forty 12-week-old male New-Zealand white rabbits were divided into group I (left untreated, n=12), group II (core decompression, n=12), and group III (core decompression + autologous EPCs implantation, n=16) after receiving an established inductive protocol for inducing steroid-associated ON. Four weeks later, these rabbits were euthanized, bilateral femora were dissected for Micro-CT-based microangiography to assess vascularization, and then the osteonecrotic changes and repair processes were examined histopathologically. Quantitative analysis showed that new vessel formation in group III was significantly greater compared with other groups at 4 weeks after treatment. The histologic and histomorphometric analyses revealed that the new bone volume was significantly higher in group III than in groups I and II 4 weeks after treatment. A combination of EPCs and core decompression enhances the neovascularization and bone regeneration in rabbit steroid-induced femoral head ON. Local implantation of EPCs may provide a novel and effective therapeutic option for early corticosteroid-induced ON.

A Fibrin Patch-Based Enhanced Delivery of Human Embryonic Stem Cell-Derived Vascular Cell Transplantation in a Porcine Model of Postinfarction Left Ventricular Remodeling

It is unknown how to use human embryonic stem cell (hESC) to effectively treat hearts with postinfarction left ventricular (LV) remodeling. Using a porcine model of postinfarction LV remodeling, this study examined the functional improvement of enhanced delivery of combined transplantation of hESC-derived endothelial cells (ECs) and hESC-derived smooth muscle cells (SMCs) with a fibrin three-dimensional (3D) porous scaffold biomatrix. To facilitate tracking the transplanted cells, the hESCs were genetically modified to stably express green fluorescent protein and luciferase (GFP/Luc). Myocardial infarction (MI) was created by ligating the first diagonal coronary artery for 60 minutes followed by reperfusion. Two million each of GFP/Luc hESC-derived ECs and SMCs were seeded in the 3D porous biomatrix patch and applied to the region of ischemia/reperfusion for cell group (MI+P+C, n = 6), whereas biomatrix without cell (MI+P, n = 5), or saline only (MI, n = 5) were applied to control group hearts with same coronary artery ligation. Functional outcome (1 and 4 weeks follow-up) of stem cell transplantation was assessed by cardiac magnetic resonance imaging. The transplantation of hESC-derived vascular cells resulted in significant LV functional improvement. Significant engraftment of hESC-derived cells was confirmed by both in vivo and ex vivo bioluminescent imaging. The mechanism underlying the functional beneficial effects of cardiac progenitor transplantation is attributed to the increased neovascularization. These findings demonstrate a promising therapeutic potential of using these hESC-derived vascular cell types and the mode of patch delivery.

Transplantation of Endothelial Progenitor Cells Improves Pulmonary Endothelial Function and Gas Exchange in Rabbits with Endotoxin-Induced Acute Lung Injury

Circulating endothelial progenitor cells (EPCs) have been therapeutically applied to aid vascular repair and myocardial regeneration. The number of circulating EPCs also provides invaluable outcome prediction for fatal diseases such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). However, evidence for the therapeutic potential of EPCs in subjects with ALI/ADRS is limited. Circulating EPCs were obtained from rabbits using Ficoll centrifugation. One week after culturing EPCs in endothelial growth medium-2, ALI was induced in rabbits by intratracheal instillation of lipopolysaccharide (500 μg/kg). Autologous EPCs or saline were administered IV after induction of ALI and animals were killed 2 days later. Pulmonary artery endothelial function and gas exchange were determined. Degrees of lung injury were assessed by alveolocapillary permeability, lung hemoglobin content, and myeloperoxidase activity. In comparison with controls, Po(2) in arterial blood was significantly elevated and pulmonary artery endothelium-dependent relaxation response was restored in rabbits receiving EPC transplantation. Lung water, Evan's blue, and bronchoalveolar lavage protein contents were significantly reduced in the EPC transplanted group, indicating a better preservation of the alveolocapillary membrane. Transplantation of EPCs decreased the lung hemoglobin level. Furthermore, expressions of CD11b and myeloperoxidase activity were also suppressed after administration of EPCs. Transplantation of EPCs restored pulmonary endothelial function, preserved integrity of the alveolocapillary barrier and suppressed the lung inflammatory response, thereby improving pulmonary gas exchange in rabbits with intratracheal lipopolysaccharide-induced ALI. Transplantation of EPCs can be a novel cell-based, endothelium-targeted therapeutic strategy for prevention and treatment of ALI/ARDS.

Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells

This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-β (TGF-β), platelet-derived growth factor-BB (PDGF-BB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 × 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-β, PDGF-BB, BDNF, GDNF and NGF. The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups. The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors.

Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction

Cardiac lymphatic system in the remodeling after acute myocardial infarction (AMI) has been overlooked. We wanted to investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) and their contribution to lymphatic distribution in myocardial remodeling after AMI. Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery and were treated with phosphate buffered saline (PBS) or EPCs. Real-time RT-PCR with 2- to 4-week myocardial tissue samples revealed that lymphangiogenetic factors such as vascular endothelial growth factor (VEGF)-C (8.5 fold, P < 0.05), VEGF-D (6.1 fold, P < 0.05), Lyve-1 (15 fold, P < 0.05), and Prox-1 (11 fold, P < 0.05) were expressed at significantly higher levels in the PBS group than the EPC group. The PBS group also showed a significantly higher density of lymphatic vessels in the peri-infarction area. Echocardiography showed that from 2 weeks after the treatment, left ventricle (LV) dimensions at both systole and diastole were significantly smaller in the EPC group than in the PBS group (P < 0.01) and LV fractional shortening was higher in the EPC group accordingly (P < 0.01). Lymphangiogenic markers increased in a mouse MI model. EPC transplantation decreased lymphangiogenesis and adverse ventricular remodeling after AMI. These novel findings suggest that new lymphatic vessels may be formed in severely damaged myocardium, and may be involved in adverse myocardial remodeling after AMI.