Development of a 3D Printed, Bioengineered Placenta Model to Evaluate the Role of Trophoblast Migration in Preeclampsia

Kuo, Che-Ying; Eranki, Avinash; Placone, Jesse K.; Rhodes, Kelly R.; Aranda‐Espinoza, Helim; Fernandes, Rohan; Fisher, John P.; Kim, Peter C.W.

doi:10.1021/acsbiomaterials.6b00031

Cited by 66 publications

(65 citation statements)

References 42 publications

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“…Similar findings were also reported for non‐dioxin‐like polychlorinated biphenyls . Recently, BeWo cells have also been employed to bioprint a 3‐D, bioengineered in vitro placenta model with biophysical properties that closely mimic those of the maternal decidua . This model was developed to capture the chemotactic effect of epidermal growth factor on the migration of trophoblasts and human mesenchymal cells for studying preeclampsia.…”

Section: Models For Placental Drug Transfersupporting

confidence: 67%

Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer

Dallmann

Liu

Burckart

et al. 2019

The Journal of Clinical Pharma

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Tremendous efforts have been directed to investigate the ontogeny of drug transporters in fetuses, neonates, infants, and children based on their importance for understanding drug pharmacokinetics. During development (ie, in the fetus and newborn infant), there is special interest in transporters expressed in the placenta that modulate placental drug transfer. Many of these transporters can decrease or increase drug concentrations in the fetus and at birth, stressing the relevance of elucidating expression in the placenta and potential gestational age‐dependent changes therein. Hence, the main objective of this review was to summarize the current knowledge about expression and ontogeny of transporters in the human placenta in healthy pregnant women. In addition, various in vitro, ex vivo, and in silico models that can be used to investigate placental drug transfer, namely, placental cancer cell lines, ex vivo cotyledon perfusion experiments, and physiologically based pharmacokinetic (PBPK) models, are discussed together with their advantages and shortcomings. A particular focus was placed on PBPK models because these models can integrate different types of information, such as expression data, ontogeny information, and observations obtained from the ex vivo cotyledon perfusion experiment. Such a mechanistic modeling framework may leverage the available information and ultimately help to improve knowledge about the adequacy and safety of pharmacotherapy in pregnant women and their fetuses.

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Section: Models For Placental Drug Transfersupporting

confidence: 67%

Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer

Dallmann

Liu

Burckart

et al. 2019

The Journal of Clinical Pharma

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“…For the invasion experiments, cells were bioprinted (2 million cells/mL) along the periphery of the cylindrical placenta model with a chemotactic source (epidermal growth factor, 10 µ M ) at the center as previously described . pECM were added at various concentration to determine its effect on invasion rates (0, 0.02, 0.2 mg/mL pECM).…”

Section: Methodsmentioning

confidence: 99%

Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three‐dimensional bioprinted placenta model

Kuo

Guo

Cabrera-Luque

et al. 2018

J Biomedical Materials Res

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Fetal cytotrophoblast invasion of maternal decidual vasculature is necessary to normal pregnancy. In preeclampsia, there is shallow invasion and abnormal remodeling of the uterine vasculature that lead to significant maternal and perinatal morbidity and mortality. The placental basement membrane (BM) proteins (e.g., laminin and collagen) has been implicated in the development of placenta while the level of laminin is significantly lower in preeclampsia. However, there are very limited studies, if any, on the effect of extracellular matrix (ECM) microenvironment on the invasion of cytotrophoblast. In this study, we hypothesized that placental BM proteins are required for effective cytotrophoblast invasion. Using proteomics, we found that more than 80% of ECM proteins in placental basal plate (pECM) were BM proteins. In addition to upregulating expressions of MMP2 (1.5-fold) and MMP9 (6.3-fold), pECM significantly increased the motility rates of cytotrophoblasts by 13-fold (from 5.60 ± 0.95 to 75.5 ± 21.8 µm/day) to achieve an effective invasion rate that was comparable to in vivo results. Treatments with PI3K inhibitors completely removed the pECM-enhanced invasive phenotypes and genotypes of cytotrophoblasts, suggesting its dominant role in cytotrophoblast-ECM interactions. Our results described, for the first time, the substantial effects of the ECM microenvironment on regulating cytotrophoblast invasion, an area that is less investigated but appear to be critical in the pathogenesis of preeclampsia. Moreover, the approach presented in this work that fabricates organ models with organ-specific ECM can be an attractive option to screen and develop novel therapeutics and biomarkers not only in preeclampsia but also other diseases such as cancer metastasis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1476-1487, 2018.

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“…3D printing has a strong potential to become a common fabrication technique in medicine as it enables fabrication of modular and patient-specific scaffolds and devices, and tissue models, with high structural complexity and design flexibility (Murphy and Atala, 2014; Jang et al, 2016a,b,c; Kang et al, 2016; Kuo et al, 2016; Zhang et al, 2016). There is a significant interest in designing novel bioink formulations toward the goal of achieving the “ideal” bioink for each bioprinting technology (Hölzl et al, 2016).…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs

Guvendiren

2017

Front. Bioeng. Biotechnol.

379

258

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There is a growing demand for alternative fabrication approaches to develop tissues and organs as conventional techniques are not capable of fabricating constructs with required structural, mechanical, and biological complexity. 3D bioprinting offers great potential to fabricate highly complex constructs with precise control of structure, mechanics, and biological matter [i.e., cells and extracellular matrix (ECM) components]. 3D bioprinting is an additive manufacturing approach that utilizes a “bioink” to fabricate devices and scaffolds in a layer-by-layer manner. 3D bioprinting allows printing of a cell suspension into a tissue construct with or without a scaffold support. The most common bioinks are cell-laden hydrogels, decellulerized ECM-based solutions, and cell suspensions. In this mini review, a brief description and comparison of the bioprinting methods, including extrusion-based, droplet-based, and laser-based bioprinting, with particular focus on bioink design requirements are presented. We also present the current state of the art in bioink design including the challenges and future directions.

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Development of a 3D Printed, Bioengineered Placenta Model to Evaluate the Role of Trophoblast Migration in Preeclampsia

Cited by 66 publications

References 42 publications

Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer

Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer

Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three‐dimensional bioprinted placenta model

Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs

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