<i>In Vitro</i>Systems for the Study of Human Placental Endocrine Function*

Ringler, Guy E.; Strauss, Jerome F.

doi:10.1210/edrv-11-1-105

Cited by 243 publications

(103 citation statements)

References 156 publications

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“…In addition, only limited morphological information is available on the initial stages of trophoblast invasion, mainly from archived specimens [12]. Until recently the best in vitro models to study the development of human placenta have been choriocarcinomaderived trophoblast cell lines, such as JAr or JEG3, and primary trophoblast cultures derived from placenta either at term or earlier in pregnancy [13]. There are shortcomings and advantages to each of these models.…”

Section: Models To Study Trophoblast Developmentmentioning

confidence: 99%

Human Embryonic Stem Cells as Models for Trophoblast Differentiation

et al. 2008

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Trophectoderm is specified from pluripotent blastomeres at some time prior to blastocyst formation. Proliferating cytotrophoblast derived from trophectoderm is the forerunner of the entire trophoblast component of the mature human placenta, including extra-villous cytotrophoblast and syncytiotrophoblast. Recently human embryonic stem cells (hESC) have been employed to study these events in an in vitro situation. Here we review some of the work in this emerging area of trophoblast biology. We concentrate primarily on a model in which colonies of hESC are exposed to BMP4 in stem cell growth medium lacking FGF2. Under both low (4 %) and high (20 %) O 2 conditions, differentiation proceeds unidirectionally towards trophoblast from the outside of the colonies inwards, with progression fastest under high O 2 . Immunohistochemical observations performed on whole colonies combined with microarray analysis of mRNA can be employed to track developmental transitions as they occur over time and in two-dimensional space as the cells respond to BMP4.

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Section: Models To Study Trophoblast Developmentmentioning

confidence: 99%

Human Embryonic Stem Cells as Models for Trophoblast Differentiation

et al. 2008

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“…For example, human placental lobe perfusion systems have shown that mechanisms of placental drug transport rates and extent can be investigated in vitro (Bassily et al, 1995;Tuntland et al, 1999;Sastry, 1999). Human trophoblast culture systems, both primary cultures and cell lines, also exist, including those that form monolayers, and have been used to study uptake and transport mechanisms at the cellular and molecular levels (Ringler and Strauss, 1990;Yui et al, 1994;Bloxam et Audus, K.L. (1999) Liu et al, 1997;Sastry, 1999).…”

Section: Approaches To Investigation Of the Human Placental Barriermentioning

confidence: 99%

“…At the cellular level, the maternal surface of the villi is covered by a layer of syncytiotrophoblasts with interspersed precursor cells called cytotrophoblasts or Langhans cells. Several cytotrophoblasts fuse or aggregate to form a multinucleated syncytiotrophoblast (Ringler and Strauss, 1990). Underlying the syncytiotrophoblast is a basement membrane shared with the endothelial cells of the fetal capillary, however, the rate-limiting barrier for permeation across the human placenta is the syncytiotrophoblast layer (Ala-Kokko et al, 1993;Sibley, 1994;Enders and Blankenship, 1999).…”

mentioning

confidence: 99%

Controlling drug delivery across the placenta

Audus

1999

European Journal of Pharmaceutical Sciences

106

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Abstract:A challenge in modern drug therapy is to develop strategies for safer and more selective targeting of drug delivery in pregnancy. Specifically, approaches are needed that would restrict unnecessary drug exposure to either mother or fetus. There is evidence emerging that indicates the placenta does express natural transport and metabolism processes that function to control drug and nutrient distribution between the mother and fetus. Further, in vitro techniques developed in the past ten years now provide some of the tools necessary to elucidate transport and metabolism processes typical of the human placenta. As a consequence, pharmaceutical scientists are in a position to contribute significantly to the design and development of drugs for pregnancy. Controlling drug delivery across the placenta: A commentary. Eur. J. Pharm. Sci. 8, 161-165. PMID: 10379038. Publisher's official version: http://dx

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“…were 80% metabolized by carboxypeptidases (46), yielding dynorphin A (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In this study, dynorphin A (1-10) was found to be insignificant amounts upon the exposure of dynorphin A (1-11) to the BeWo cells, suggesting that aminopeptidases are the major enzymes in this cell type.…”

Section: Stability Of Opioid Peptides Upon Exposure To Bewo Cell Monomentioning

confidence: 58%

“…for glucose, fatty acids and amino acids) have been identified (10,11). Several in vivo and in vitro models have been utilized to study the transport of substances across the placental barrier (12,13). However, in vitro models provide a simple and rapid method of studying the mechanistic aspects of drug transport.…”

Section: Introductionmentioning

confidence: 99%

Transport and metabolism of opioid peptides across BeWo cells, an in vitro model of the placental barrier

Ampasavate¹,

Chandorkar²,

Velde³

et al. 2002

International Journal of Pharmaceutics

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. (2002) Transport and metabolism of opioid peptides across BeWo Cells, an in vitro model of the placental barrier. Int. J. Pharm. 233,[85][86][87][88][89][90][91][92][93][94][95][96][97][98] Abstract: In keeping with the advance of biotechnology, cell culture becomes an important tool for investigating the transport and the metabolism phenomena. A cell line of human origin, the BeWo choriocarcinoma cell line, was used for the study of the transport and metabolism of opioid peptides across the in vitro model of the placental barrier. Opioid peptides, both naturally occurring and their synthetic analogs, are of interest to be developed as potent analgesics and were included in this study. The apparent permeability coefficients of the peptides containing 4 to 11 amino acid or analog residues were in the range of 0.23-14.60 x 10 -5 cm/sec. The apparent permeability coefficients of these peptides were comparable to those of sucrose or dextrans, hydrophilic markers. Molecular weight and size of the peptides were inversely correlated to the permeability across the BeWo monolayers. Lipophilicity and charges of the peptides were also investigated and found to be the minor factors regulating the extent of peptide permeation. Contrasting to the transport of DPDPE peptide analog across the blood-brain barrier, the transport of DPDPE across the BeWo monolayers were not found to be via carrier-mediated transport. The major transport pathway of the opioid peptides across the BeWo monolayers was found to be via paracellular route. In metabolism studies, aminopeptidase was found to be a major enzyme type responsible for the degradation of naturally occurring peptides but not for the synthetic analogues. The finding obtained from the present study reveal the applicability of the BeWo cell line to be used as the in vitro cell culture model for the transport and metabolism screening of the opioid peptides.

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In VitroSystems for the Study of Human Placental Endocrine Function*

Cited by 243 publications

References 156 publications

Human Embryonic Stem Cells as Models for Trophoblast Differentiation

Human Embryonic Stem Cells as Models for Trophoblast Differentiation

Controlling drug delivery across the placenta

Transport and metabolism of opioid peptides across BeWo cells, an in vitro model of the placental barrier

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