Pei-Chun Chen

Mackay Memorial Hospital, T’ai-pei, Taipei, Taiwan

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Publications (7)26.3 Total impact

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    ABSTRACT: Introduction: The effects of nanoparticles on pregnancy remain unclear. In this study, we investigate whether nanoparticles of a specific size can cross the placenta and affect trophoblast function. Methods: Fluorescently labelled carboxylate-modified polystyrene beads with diameters of 20, 40, 100, 200, and 500 nm were chosen as model particles. In vitro, trophoblast cell line (3A-Sub-E) or primary culture of term trophoblasts was used for nanoparticle uptake analysis using flow cytometry, confocal microscopy, BrdU proliferation assay and analysis of cell apoptosis using Western blot. Intravenous injection of nanoparticles into pregnant mice at embryonic day 17 was used to study whether nanoparticles can cross the placenta. The mouse placentas were collected and quantitatively analyzed using high-performance liquid chromatography for nanoparticle uptake. Results: Fluorescent polystyrene particles with diameters of up to 500 nm were taken up by the placenta and were able to cross the placental barrier. The fluorescent polystyrene particles were observed in various organs of fetuses after 4 h of administration to pregnant mice. The nanoparticle uptake by placental tissue was significantly increased in nanoparticles with a diameter of 40 nm. No linear association was evident between nanoparticle size and uptake. Nanoparticles with diameters of 20 nm (200 μg/ml) and 40 nm (500 μg/ml) could induce trophoblast cell apoptosis with increased cleaved caspase 3 and reduced cell proliferation. Discussion: Our findings suggest that nanoparticles can cross the placenta and be taken up by fetal organs. Certain concentrations of carboxylate-modified polystyrene nanoparticles may be cytotoxic to trophoblasts, which could alter placental function.
    Placenta 10/2015; DOI:10.1016/j.placenta.2015.10.007 · 2.71 Impact Factor
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    ABSTRACT: We aim to study the smooth muscle cell differentiation capability of human placental multipotent mesenchymal stromal cells (hPMSCs) and to identify how endothelial cells recruit hPMSCs participating in vessel formation. hPMSCs from term placentas were induced to differentiate into smooth muscle cells in induction conditions and different matrix substrates. We assessed endothelial cells from umbilical veins for PDGF-BB expression and to induce hPMSC PDGFR-beta and STAT3 activation. Endothelial cells were co-cultured with hPMSCs for in vitro angiogenesis. Cell differentiation ability was then further assessed by mouse placenta transplantation assay. hPMSCs can differentiate into smooth muscle cells; collagen I, IV or laminin supports this differentiation. Endothelial cells expressed significant levels of PDGF-BB and activated STAT3 transcriptional activity in hPMSCs. Endothelial cell conditioned medium induced hPMSC migration, which was inhibited by STAT3 siRNA transfection or PDGFR-beta blocking antibody pretreatment, but not by PDGFR-alpha blocking antibody or isotype IgG (p<0.001). hPMSCs can incorporate into endothelial cells with tube formation and promote endothelial cells forming capillary-like networks than endothelial cells alone (tube length: 12024.1 ± 960.1 vs. 9404.2 ± 584.7 pixels; p < 0.001). The capillary-like networks were significantly reduced by hPMSCs pretreated with PDGFR-beta blocking antibody, but not by PDGFR-alpha blocking antibody or isotype IgG (p<0.001). Transplantation of hPMSCs into mouse placentas revealed incorporation of the hPMSCs into vessel walls, which expressed alpha-smooth muscle actin, calponin, and smooth muscle myosin (heavy chain) in vivo. In conclusion, endothelial cell-hPMSC interactions occur during vessel development of placenta. Endothelial cell-derived PDGF-BB recruits hPMSCs involved in vascular development via PDGFR-beta/STAT3 activation.
    Biology of Reproduction 09/2015; DOI:10.1095/biolreprod.115.131250 · 3.32 Impact Factor
  • Chie-Pein Chen · Yi-Yung Chen · Chang-Ching Liu · Pei-Chun Chen ·

    Placenta 09/2013; 34(9):A45. DOI:10.1016/j.placenta.2013.06.136 · 2.71 Impact Factor
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    ABSTRACT: Human placental multipotent mesenchymal stromal cells (hPMSCs) can be isolated from term placenta, but their angiogenic ability and the regulatory pathways involved are not known. hPMSCs were shown to express integrins alpha(v), alpha(4), alpha(5), beta(1), beta(3), and beta(5) and could be induced to differentiate into cells expressing endothelial markers. Increases in cell surface integrins alpha(5) and beta(1), but not alpha(4), alpha(v)beta(3), or alpha(v)beta(5), accompanied endothelial differentiation. Vascular endothelial growth factor-A augmented the effect of fibronectin in enhancing adhesion and migration of differentiated hPMSC through integrin alpha(5)beta(1), but not alpha(v)beta(3) or alpha(v)beta(5). Formation of capillary-like structures in vitro from differentiated cells was inhibited by pre-treatment with function-blocking antibodies to integrins alpha(5) and beta(1). When hPMSCs were seeded onto chick chorioallantoic membranes (CAM), human von Willebrand factor-positive cells were observed to engraft in the chick endothelium. CAMs transplanted with differentiated hPMSCs had a greater number of vessels containing human cells and more incorporated cells per vessel compared to CAMs transplanted with undifferentiated hPMSCs, and overall angiogenesis was enhanced more by the differentiated cells. Function-blocking antibodies to integrins alpha(5) and beta(1) inhibited angiogenesis in the CAM assay. These results suggest that differentiated hPMSCs may contribute to blood vessel formation, and this activity depends on integrin alpha(5)beta(1).
    PLoS ONE 10/2009; 4(10):e6913. DOI:10.1371/journal.pone.0006913 · 3.23 Impact Factor

  • PLoS ONE 01/2009; 4(10). DOI:10.1371/journal.pone.0006913.g006 · 3.23 Impact Factor
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    ABSTRACT: Human placental mesenchymal stem cells (hPMCs) are thought to be multipotent, but their fate after in utero transplantation is not known. hPMCs isolated from term placenta were assessed for their phenotype markers, mutilineage capacity, and immunomodulatory properties. Their engraftment potential was analyzed in a pregnant rat model after in utero transplantation at embryonic day 17. Immunohistochemistry, tracing of labeled cells, fluorescence in situ hybridization and real-time PCR were used to assess post-transplant chimerism. In vitro, lineage-negative, CD34-negative hPMCs differentiated into osteocytes, adipocytes, hepatocytes and endothelial cells with tube formation, and actively suppressed the rat lymphocyte proliferative response to allogeneic lymphocyte stimulation (P < 0.0001). After in utero transplantation into pregnant rats, a low level of engraftment was achieved in various fetal tissues. Engraftment occurred in more than 60% of the fetal rats. Cells persisted for at least 12 weeks after delivery and evidence was obtained to suggest differentiation into specific lineages, including hepatocytes and hematopoietic cells. However, a greater number of hPMCs migrated to the placenta than to the fetus, thus limiting the degree of cell engraftment in fetal organs. We conclude that hPMCs are mutipotent cells that can be engrafted long-term in immunocompetent rats after in utero transplantation.
    Human Reproduction 10/2008; 24(1):154-65. DOI:10.1093/humrep/den356 · 4.57 Impact Factor
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    ABSTRACT: Maternal cells can become engrafted in various fetal organs during pregnancy. The nature of the cells and the mechanisms of maternofetal cell trafficking are not clear. We demonstrate that human lineage-negative, CD34-negative (Lin(-)CD34(-)) multipotent mesenchymal stromal cells express alpha(2), alpha(4), alpha(5), and beta(1) integrins, which mediate their adhesion to endothelium, and vascular endothelial growth factor receptor-1 (VEGFR-1), which mediates their response to vascular endothelial growth factor A (VEGF-A). A maternal-fetal VEGF-A concentration gradient exists across the placental barrier, and cord blood plasma induces transendothelial and trans-Matrigel migration of stem cells in vitro. Migration is inhibited by a VEGF-A-neutralizing antibody or antibodies against VEGFR-1 or integrin alpha(2), alpha(4), alpha(5), or beta(1). When Lin(-)CD34(-) multipotent mesenchymal stromal cells are transferred to rat maternal venous blood, they traffic through the placenta, engraft in various fetal organs, and persist in offspring for at least 12 weeks. Cell proliferation ability is retained in the xenogeneic placenta. Maternofetal trafficking is significantly reduced by blocking antibodies against integrins alpha(2), alpha(4), alpha(5), and beta(1) or VEGFR-1. These results suggest that maternal microchimerism arises by the trafficking of multipotent mesenchymal stromal cells via VEGF-A- and integrin-dependent pathways across the hemochorial placenta to fetal tissues.
    Stem Cells 03/2008; 26(2):550-61. DOI:10.1634/stemcells.2007-0406 · 6.52 Impact Factor