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Table 2 Organ-on-a-chip for studying pregnancy-related phenomena (focusing on placenta-on-a-chip)

From: Organ-on-a-chip: future of female reproductive pathophysiological models

Model category

Cell types

Culture environment

Device characteristics

Culture characteristics

Significance

Year/Reference

Placenta-on-a-Chip

λ Human trophoblasts (JEG-3)

λ HUVECs

λ Medium: JEG-3: DMEM + 10% FBS + 1% penicillin/streptomycin; HUVECs: EBMTM-2 basal medium + Endothelial Cell Growth Medium-2 MV Bullet Kit

λ Temperature: 37 °C; CO2: 5%

λ Two PDMS slabs containing microchannel features: 500 μm × 200 μm (width × height)

λ A vitrified collagen membrane

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 30 µl/h

λ Coating: 40 µg/ml of fibronectin and 1.5% gelatin

Transport function of placental barrier—lucos transport

2016/ [16]

Placenta-on-a-Chip

λ Human trophoblasts (BeWo)

λ HUVECs

λ Medium: Bewo: Ham’s F-12 K + 10% FBS + 40 µg/mL gentamicin; HUVECs: endothelial cell growth medium kit

λ Two PDMS microchannels features: 1 mm× 200 μm (width × height)

λ A polycarbonate membrane containing 400 nm pores

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 2 µl/h

λ Coating: collagen I

Transport function of placental barrier—glucose transport

2020/ [86]

Placenta-on-a-Chip

λ Human trophoblasts (BeWo)

λ HPVECs

λ Medium: BeWo: DMEM/F-12 K + 10% FBS + 1% L-glutamine + 1% penicillin/streptomycin; HPVECs: EGM-2 medium + 2% FBS

λ Temperature: 37 °C; CO2: 5%

λ Two PDMS slabs containing microchannel features: 1.5 cm×1 mm×135 μm

λ A vitrified collagen membrane

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 100 µl/h

λ Coating: 0.1 mg/ml human fibronectin solution

Transport function of placental barrier—glucose transport

2016/ [87]

Placenta-on-a-Chip

λ Ditto

λ Ditto

λ Ditto

λ Ditto

Transport function of placental barrier—drug transport (Glyburide)

2018/ [88]

Placenta-on-a-Chip

λ Ditto

λ Medium: BeWo: Ham’s F-12 K + 10% FBS; HUVECs: EBM + endothelial cell growth supplement + FBS

λ Temperature: 37 °C; CO2: 5%

λ Two PDMS slabs containing microchannel features: 400 μm × 100 μm (width × height)

λ A 0.4micron pore-sized polyester track etched membrane

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 50 µl/h

λ Coating: /

Transport function of placental barrier—caffeine transport

2019/ [89]

Fetal membrane decidua-on-a-Chip (FMi-OOC) and placenta-on-a-Chip (PLA-OOC)

λ Human decidua and fetal membrane cell

λ Human placenta cell line

λ Medium: DEC: DMEM/F-12 + 10% FBS + 10% penicillin/streptomycin + 10% amphotericin B; AEC: KSFM medium + 30 µg/mL bovine pituitary extract + 0.1ng/mL epidermal growth factor + 0.4 mM CaCl2 + 0.5 mg/mL primocin; AMC + CMC: DMEM/F-12 + 5% FBS + 10% penicillin/streptomycin + 10% amphotericin B; CTC: DMEM/F-12 + 0.20% FBS + 0.1 mM β-mercaptoethanol + 0.5% penicillin/streptomycin + 0.3% BSA + 1× ITS-X + 2 µM CHIR99021 + 0.05 µM A83-01 + 1.5 µg/mL l-ascorbic acid + 50 ng/mL epithelial growth factor + 0.08 mM VPA + 1× Revitacell

λ Temperature: 37 °C; CO2: 5%

λ FMi-OOC: four concentric-shaped culture compartments (one for maternal cells and three for fetal cells)

λ PLA-OOC: STB + CTB + HUVEC chambers: 250 μm in height

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: type IV basement membrane collagen Matrigel and collagen type 1

Transport function of placental barrier—drug transport and metabolism (Statin)

2022/ [90]

Placental barrier on-a-chip

λ Human trophoblasts (BeWo)

λ HPVECs

λ Medium: BeWo: DMEM + 10% FBS + 1% penicillin-streptomycin; HUVECs: complete human endothelial cell medium

λ Temperature: 37 °C; CO2: 5%

λ The top and bottom perfusion lanes features: 300 μm × 220 μm (width × height)

λ The middle lane features: 350 μm × 220 μm (width × height)

λ A meniscus pinning barrier

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: /

Transporter function, barrier function and hormone secretion

2023/ [94]

Placenta-on-a-chip

λ Ditto

λ Medium: BeWo: DMEM/F-12 + 15% FBS + 1× L-Glutamine + 1% penicillin-streptomycin; HUVECs: ECM medium

λ Temperature: 37 °C; O2: 95%; CO2: 5%

λ The top and bottom microchannels features: 2 mm×350 μm×200 μm

λ The middle matrix channel features: 2 mm×300 μm×50 μm

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 20 µl/h

λ Coating: Collage I

Barrier function of placental—TiO2 NPs

2019/ [96]

Placental Nanoparticle Uptake-On-a-Chip

λ BeWo

λ Medium: BeWo: Ham’s F-12 K + 10% FBS + 1% L-Glutamine + 1% penicillin–streptomycin–neomycin

λ Temperature: 37 °C; CO2: 5%

λ The microfluidic channel: 50 mm×5 mm×450 μm

λ Device material: /

λ Fabrication method: /

λ Flow rate: 22.89µL/min

λ Coating: gelatin

Barrier function of placental—Placental Nanoparticle Uptake

2022/ [98]

Placenta-on-a-Chip

λ Human trophoblasts (BeWo)

λ HVTs

λ Medium: BeWo: Ham’s F-12 + 10% FBS + 50 µg/ml kanamycin sulfate; HVTs: trophoblast medium + FBS + trophoblast growth factors

λ Temperature: 37 °C; CO2: 5%

λ The upper layer channel: 15 mm×2 mm×200 μm

λ The bottom layer channel: 20 mm×2 mm×200 μm

λ The VC membrane: 10 μm thickness

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 5 µl/h

λ Coating: /

Intrusion function: to provide molecular insight into the microvilli-mediated mechanoresponsive cellular functions

2015/ [104]

Placenta-on-a-Chip

λ Human trophoblast cells

λ dNK cells

λ Medium: tophoblast cells: DMEM + 20% FCS + 1 mM sodium pyruvate + 1× MEM non-essential amino acids + 2 mM L-glutamine, 10 units/ml penicillin + 100 µg/ml streptomycin + 2 mg/ml gentamycin; dNK cells: RPMI1640 + antibiotics + 10% FCS and 2.5 ng/ml IL-15

λ Temperature: 37 °C; CO2: 5%

λ The dimensions of each device: 4.5 × 2.3 cm with the length, width and height of each channel of 20 300 μm, 1300 μm and 150 μm respectively

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 50 µl/h

λ Coating: Matrigel

Intrusion function: to quantify the migratory characteristics of primary trophoblast cells to model EVT migration

2017/ [105]

Placenta-on-a-Chip

λ Human first trimester placenta cells (HTR8/SVneo)

λ HUVECs

λ Medium: HTR8/SVneo: DMEM/F-12 + 1% penicillin–streptomycin + 2 mM L-glutamine + 10% FBS + 10 mM HEPES; HUVECs: complete medium + EGM-2 Plus medium

λ Temperature: 37 °C; CO2: 5%

λ The center of the 3D microfluidic chip with the central compartment, outer channels (width: 200 μm), and pillar barrier (width: 50 μm), filled with pillars (pillar spacing: 3 μm)

λ Device material: PDMS

λ Fabrication method: /

λ Flow rate: 0.01/0.05/0.1 µl/min

λ Coating: extracellular matrix

Intrusion function: to recreate the placental invasion microenvironment

2021/ [106]

Placenta-on-a-Chip

λ hiPSC

λ Medium: mTeSR1 medium

λ Temperature: 37 °C; CO2: 5%

λ The first layer: PMMA, 90 × 50 × 4 mm3

λ The second layer: PDMS, 76 × 26 × 4 mm3

λ The third layer: PDMS, 76 × 26 × 1.5 mm3

λ The fourth layer: PMMA, 90 × 50 × 5 mm3

λ Device material: PMMA and PDMS

λ Fabrication method: laser cutting and customized cutting die technology

λ Flow rate: 1 ml/min

λ Coating: 0.5 mm thick Matrigel

Intrusion function: to create an in vitro placental trophoblast-like model with major cell types of the human placenta, including CTBs, differentiated subtypes, STBs, and EVTs

2022/ [107]

Placenta-on-a-Chip

λ hTSCs

λ Medium: hTSCs: TS medium + DMEM/F-12 + 0.1 mM 2-mercaptoethanol + 0.2% FBS + 0.5% Penicillin–Streptomycin + 0.3% HAS + 1% ITS-X supplement + 1.5 mg/mL L-ascorbic acid + 50 ng/mL EGF + 2 mM CHIR99021 + 0.5 mM A83-01 + 1 mM SB431542 + 0.8 mM VPA + 5 mM Y27632; HUVECs: Collagen I-coated plates and maintained in endothelial cell medium (ECM)

λ Temperature: 37 °C; CO2: 5%

λ The upper and lower layers with microchannel: 20 × 1.2 × 0.2mm3

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 10µL/h

λ Coating: hTSCs: Collagen IV; HUVECs: Collagen I

Intrusion function: to describe a biomimetic placental barrier model of hTSCs in a perfused organ chip system

2023/ [108]

  1. Notes: HVTs, human villous trophoblasts; HUVECs, human umbilical vein endothelial cells; DMEM, Dulbecco’s Modified Eagle Medium; FBS, fetal bovine serum; HPVECs: Human primary placental villous endothelial cells; EBM, endothelial basal medium; DEC: decidua parietalis cells; AEC: amnion epithelial cells; AMC: amnion mesenchymal cells; CMC: chorion mesenchymal cells; CTC: chorion trophoblast cells; ECM, endothelial cell medium; FCS: fetal calf serum; IL-15, Interleukin 15; EVT, extra villous trophoblast; PMMA, polymethyl methacrylate; hiPSC, Human Pluripotent Stem Cell; CTBs, trophoblast progenitor cytotrophoblasts; STBs, syncytiotrophoblasts; hTSCs, human trophoblast stem cells