Distribution, function and pathologic impacts of cardiac lymphatic vessels / 解剖学报

Drainage of lymph plays an important role in maintaining homeostasis of the myocardium. In heart diseases such as myocardial infarction and heart failure, injure or dysfunction of the lymphatic vessels result in cardiac lymphedema, leading to cardiac fibrosis, inflammation and cardiac dysfunction. In recent years, more attention has been put on studying relation of cardiac lymphedema with heart diseases and physiopathologic impacts of cardiac lymphangiogenesis. Targeting cardiac lymphangiogenesis is regarded as a feasible therapy for relieving cardiac lymphedema. However, the optimized strategies to sustainedly release growth factors or drugs and to transplant stem / progenitor cells need to be investigated. This article reviews mainly the characteristics of the distribution and function of the cardiac lymphatic vessels, and discusses the pathologic affects of cardiac lymphedema, the mechanisms of cardiac lymphangiogenesis and clinical impacts of promoting cardiac lymphangiogenesis.

Sorting of lymphatic endothelial progenitor cells from canine peripheral blood and their differentiation induction towards endothelial cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the biological properties of CD34+/CD133 +/VEGFR-3 + lymphatic endothelial progenitor cells in peripheral blood and explore the effects of the VEGF-C/VEGFR-3 signaling pathway on differentiation of lymphatic endothelial progenitor cells to lymphatic endothelial cells.</p><p><b>METHODS</b>Mononuclear cells were isolated from peripheral blood by density centrifugation with Percoll solution, and VEGFR-3+ cells were sorted from them with flow cytometry. Differentiation of VEGFR-3+ cells was induced with VEGF-C. The morphology and ultrastructures of the cells were observed with scanning and transmission electron microscopes. Expression of surface markers were examined with a confocal laser scanning microscope.</p><p><b>RESULTS</b>VEGFR-3+ cells expressed CD34 and CD133 antigen. The percentage of CD34+/ VEGFR-3+ and VEGFR-3+/CD133+ cells were 0.13% and 0.08% of peripheral blood MNC respectively. The size of CD34+/CD133+/VEGFR-3+ cells was about 15 microm in the diameter. After induction with VEGFC, they were increased. The cells were shuttle-like in shape and extended the lamellipodia and many filopodia. After 1 week induction with VEGF-C, they expressed coagulation factor VII related antigen, and at 2 week induction, they showed caveolae on the surface and Weibel-Palade body inside the cells. The specific lymphatic endothelial marker LYVE-1 was expressed on the cells, and no longer expressed CD133.</p><p><b>CONCLUSIONS</b>CD34+/CD133+/VEGFR-3+ lymphatic endothelial progenitor cells from peripheral blood may differentiate into lymphatic endothelial cells. The VEGF-C/VEGFR-3 signaling pathway has important effects on the differentiation of the lymphatic endothelial progenitor cells.</p>

Effects of marrow-derived cardiac stem cell transplantation after myocardial infarction in rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic potential of marrow-derived cardiac stem cell (MCSC) transplantation after myocardial infarction (MI) in rats.</p><p><b>METHODS</b>MCSC were selected from the marrow mesenchymal stem cell (MMSC) of male SD rats by single-cell cloning culture. MI was induced by left anterior descending artery ligating in female SD rats. Equal volume PBS, MMSC and MCSC were transplanted at the border zone of the infarct one week after MI. Cardiac function was assessed by echocardiography at four weeks after cell transplantation. The hearts were removed and morphological changes of scar tissue were examined with HE staining and Masson trichrome staining, VEGFR-1(+) capillary vessels were labeled with immunohistochemical staining. Scar area and vessel density were measured by image analyzer. MCSC containing Y chromosome were examined using in situ fluorescent hybridization, and cardiomyocyte cTnT expression was also analyzed.</p><p><b>RESULTS</b>Cardiac transcription factor Nkx2.5 was expressed at low level in c-kit(+) MCSC. Four weeks after cell transplantation, left ventricular fractional shortening and ejection fraction were significantly higher while scar area was significantly lower in MCSC group compared to MMSC group and control group. cTnT was expressed in cells containing Y chromosome and these cells were connected with myocardium of recipient rats in the rats transplanted with MCSC. Vessel density around the infarcted tissue in MCSC group was similar as that in MMSC group and significantly higher than that in control group.</p><p><b>CONCLUSION</b>MSCS could effectually differentiate into functional cardiomyocytes at the border zone of the infarct, and MCSC transplantation post MI significantly improved cardiac functions and promoted angiogenesis.</p>

Establishment of coculture model of blood-brain barrier in vitro for nanoparticle's transcytosis and toxicity evaluation / 药学学报

<p><b>AIM</b>A method of coculture of brain capillary endothelial cells (BCECs) and astrocytes of rats was used to evaluate nanoparticle's blood-brain barrier (BBB) transcytosis and toxicity at the endothelial tight junction.</p><p><b>METHODS</b>A lipophilic fluorescent probe, 6-coumarin, was incorporated in poly (ethyleneglycol)-poly (lactide) nanoparticle using double emulsion/solvent evaporation method. BCECs and astrocytes were firstly isolated from brain of newborn rats and characterized by their morphology and immunocytochemistry staining, separately. Subsequently, a coculture model with BCECs on the top of micro-porous membrane of cell culture insert and astrocytes on the bottom side was established. The permeability of 14C-labeled sucrose and nanoparticle were determined, separately.</p><p><b>RESULTS</b>The mean weight-based diameter of 6-coumarin loaded nanoparticles was (102.4 +/- 6.8) nm, with zeta potential of (-16.81 +/- 1.05) mV. BCECs were positive for factor VIII staining and glial fibrillary acidic protein was expressed in astrocytes. The transendothelial electrical resistance reached up to (313 +/- 23) omega x cm2. The tight junction between BCECs in the coculture model could be visualized by both scanning electron microscopy and transmission electron microscopy. The unchanged paracellular transport of sucrose proved that nanoparticle with concentration lower than 200 microg x mL(-1) did not impact the integrity of BBB endothelial tight junctions. The permeability of 10 microg x mL(-1) 6-coumarin labeled nanoparticle was 0.29 x 10(-3) cm x min(-1).</p><p><b>CONCLUSION</b>This in vitro experimental model of rat BBB was close to resemble the in vivo situation for examination of the permeability of nanoparticle and toxicity evaluation.</p>