Ji Soo Lee1, Roberto Romero2,3,4,5, Yu Mi Han6, Hee Chan Kim7,8,9, Chong Jai Kim10, Joon-Seok Hong6, Dongeun Huh11. 1. a Interdisciplinary Program of Bioengineering, Seoul National University Graduate School , Seoul , Republic of Korea . 2. b Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development , NIH, Bethesda, MD and Detroit, MI , USA . 3. c Department of Obstetrics and Gynecology , University of Michigan , Ann Arbor , MI , USA . 4. d Department of Epidemiology and Biostatistics , Michigan State University , East Lansing , MI , USA . 5. e Department of Molecular Obstetrics and Genetics , Wayne State University , Detroit , MI , USA . 6. f Department of Obstetrics and Gynecology , Seoul National University Bundang Hospital , Gyeonggi-do , Republic of Korea . 7. g Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University , Seoul , Republic of Korea . 8. h Department of Biomedical Engineering , Seoul National University College of Medicine , Seoul , Republic of Korea . 9. i Department of Biomedical Engineering , Seoul National University Hospital , Seoul , Republic of Korea . 10. j Department of Pathology , Asan Medical Center, University of Ulsan College of Medicine , Seoul , Republic of Korea , and. 11. k Department of Bioengineering , University of Pennsylvania , Philadelphia , PA , USA.
Abstract
OBJECTIVE: Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta. MATERIALS AND METHODS: A "Placenta-on-a-Chip" microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone. RESULTS: Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations. CONCLUSION: The "Placenta-on-a-Chip" microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.
OBJECTIVE: Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta. MATERIALS AND METHODS:A "Placenta-on-a-Chip" microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone. RESULTS: Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations. CONCLUSION: The "Placenta-on-a-Chip" microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.
Authors: R A Pattillo; G O Gey; E Delfs; W Y Huang; L Hause; D J Garancis; M Knoth; J Amatruda; J Bertino; H G Friesen; R F Mattingly Journal: Ann N Y Acad Sci Date: 1971-01-28 Impact factor: 5.691
Authors: Robert N Carter; Stephanie M Casillo; Andrea R Mazzocchi; Jon-Paul S DesOrmeaux; James A Roussie; Thomas R Gaborski Journal: Biofabrication Date: 2017-02-14 Impact factor: 9.954
Authors: Yu Shrike Zhang; Julio Aleman; Su Ryon Shin; Tugba Kilic; Duckjin Kim; Seyed Ali Mousavi Shaegh; Solange Massa; Reza Riahi; Sukyoung Chae; Ning Hu; Huseyin Avci; Weijia Zhang; Antonia Silvestri; Amir Sanati Nezhad; Ahmad Manbohi; Fabio De Ferrari; Alessandro Polini; Giovanni Calzone; Noor Shaikh; Parissa Alerasool; Erica Budina; Jian Kang; Nupura Bhise; João Ribas; Adel Pourmand; Aleksander Skardal; Thomas Shupe; Colin E Bishop; Mehmet Remzi Dokmeci; Anthony Atala; Ali Khademhosseini Journal: Proc Natl Acad Sci U S A Date: 2017-03-06 Impact factor: 11.205