SHORT COMMUNICATION: Development of a Human Model to Study Homing Behavior of Immune Cells into Decidua and Placental Villi Under <i>Ex Vivo</i> Conditions

Heinzelmann, Joana; Enke, Uta; Seyfarth, Lydia; Schleußner, E; Malek, Antoine; Markert, Udo R.

doi:10.1111/j.1600-0897.2008.00666.x

Cited by 6 publications

(6 citation statements)

References 27 publications

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“…In this perfusion system, migrating CMSC29 and DMSC23 cells crossed the endothelial barrier within as little as 3 hours and remained in a location consistent with the MSC niche adjacent to endothelial cells even after 4 days of incubation. This contrasts with the results seen with other cells, for example, when labelled maternal lymphocytes were perfused into the maternal-side of the placenta, the lymphocytes crossed the endothelial barrier, migrated through the stroma and infiltrated the fetal villous structures (15). A possible explanation for the migration pattern of cells in this perfusion system is that there was no damage to the perfused tissue, and thus, the MSCs did not receive the appropriate damage signal to promote their movement into the tissue stroma, and instead remained in their niche.…”

Section: Discussioncontrasting

confidence: 93%

“…Cells suspended in supplemented medium were seeded into 6-well plates and left to adhere and grow overnight. Five wells per plate were seeded, one for each concentration tested (15,20,25,30 and 35 µM). Five plates in total were used, one for each incubation time tested (0.5, 1, 1.5, 2 and 2.5 hours).…”

Section: Optimizing Live-cell Fluorescent Labelling For Cmsc29 and Dmmentioning

confidence: 99%

“…Perfusion of the human placenta is one of the most useful methods to examine the transplacental transfer of chemical substances and drugs through the maternalfetal interface (10)(11)(12)(13). The placental perfusion model has also been used to investigate the transplacental transfer of antigens, such as the blood stage malaria antigen (14), or to study the transfer of immune cells from the mother to the fetus (15), and the invasion of leukaemia cells into fetal tissues (16).…”

Section: Introductionmentioning

confidence: 99%

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An ex vivo human placental vessel perfusion method to study mesenchymal stem/stromal cell migration

et al. 2019

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Background: To initiate tissue repair, mesenchymal stem/stromal cells (MSCs) must enter the blood stream, migrate to the targeted area, cross the endothelial barrier and home to the damaged tissue. This process is not yet fully understood in humans and thus, the aim of this study was to develop an ex vivo placental vessel perfusion method to examine human MSC movement from a blood vessel into human tissue. This will provide a better understanding of MSC migration, movement through the endothelial barrier and engraftment into target tissue, in a setting that more closely represents the in vivo state, compared with conventional in vitro human cell culture models. Moreover, important similarities and differences to animal experimental model systems may be revealed by this method. Methods: Human placental hTERT transformed MSC lines were labelled with live-cell fluorescence dyes, and then perfused into term human placental blood vessel. After labelled MSCs were perfused into the vessel, the vessel was dissected from the placenta and incubated at cell growth conditions. Following incubation, the vessel was washed thoroughly to remove unattached, labelled MSCs and then snap frozen for sectioning. After sectioning, immunofluorescence staining of the endothelium was carried out to detect if labelled MSCs crossed the endothelial barrier. Results: Twelve placental vessel perfusions were successfully completed. In eight of the twelve perfused vessels, qualitative assessment of immunofluorescence in sections (n=20, 5 µm sections/vessel) revealed labelled MSCs had crossed the endothelial barrier. Conclusions: The human placental ex vivo vessel perfusion method could be used to assess human MSC migration into human tissue. Cells of the MSC lines were able to adhere and transmigrate through the endothelial barrier in a manner similar to that of leukocytes. Notably, cells that transmigrated remained in close proximity to the endothelium, which is consistent with the reported MSC vascular niche in placental blood vessels.

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Section: Discussioncontrasting

confidence: 93%

Section: Optimizing Live-cell Fluorescent Labelling For Cmsc29 and Dmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An ex vivo human placental vessel perfusion method to study mesenchymal stem/stromal cell migration

et al. 2019

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“…The perfusion with oxygenized and warmed (37°C) medium maintains the tissue vital for more than 8 hr. The system can be used to test the deposition of instilled substances or cells in the placental tissue and the potential toxic effects therein (Heinzelmann et al 2009). …”

Section: Single Maternal Side Placenta Perfusionmentioning

confidence: 99%

“…The way of exposure to toxicants and washing out of secretions via perfusion is more natural than in explant cultures. Histological assessment allows a wider overview than that of explants (Heinzelmann et al 2009). Accumulation of toxicants or their fragments in the tissue or in defined compartments or cell types can be perceived depending on the nature of the toxic agent and the available detection systems.…”

Section: Single Maternal Side Placenta Perfusionmentioning

confidence: 99%

The Placenta in Toxicology. Part IV

Göhner

Svensson‐Arvelund

Pfarrer³

et al. 2013

Toxicol Pathol

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This review summarizes the potential and also some limitations of using human placentas, or placental cells and structures for toxicology testing. The placenta contains a wide spectrum of cell types and tissues, such as trophoblast cells, immune cells, fibroblasts, stem cells, endothelial cells, vessels, glands, membranes, and many others. It may be expected that in many cases the relevance of results obtained from human placenta will be higher than those from animal models due to species specificity of metabolism and placental structure. For practical and economical reasons, we propose to apply a battery of sequential experiments for analysis of potential toxicants. This should start with using cell lines, followed by testing placenta tissue explants and isolated placenta cells, and finally by application of single and dual side ex vivo placenta perfusion. With each of these steps, the relative workload increases while the number of feasible repeats decreases. Simultaneously, the predictive power enhances by increasing similarity with in vivo human conditions. Toxic effects may be detected by performing proliferation, vitality and cell death assays, analysis of protein and hormone expression, immunohistochemistry or testing functionality of signaling pathways, gene expression, transport mechanisms, and so on. When toxic effects appear at any step, the subsequent assays may be cancelled. Such a system may be useful to reduce costs and increase specificity in testing questionable toxicants. Nonetheless, it requires further standardization and end point definitions for better comparability of results from different toxicants and to estimate the respective in vivo translatability and predictive value.

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