title: Placenta-on-a-chip: a novel platform to study the biology of the human placenta.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: a Interdisciplinary Program of Bioengineering, Seoul National University Graduate School , Seoul , Republic of Korea .
authors.forename: Ji Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: 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 .|c Department of Obstetrics and Gynecology , University of Michigan , Ann Arbor , MI , USA .|d Department of Epidemiology and Biostatistics , Michigan State University , East Lansing , MI , USA .|e Department of Molecular Obstetrics and Genetics , Wayne State University , Detroit , MI , USA .
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: f Department of Obstetrics and Gynecology , Seoul National University Bundang Hospital , Gyeonggi-do , Republic of Korea .
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Han
authors.affiliation: g Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University , Seoul , Republic of Korea .|h Department of Biomedical Engineering , Seoul National University College of Medicine , Seoul , Republic of Korea .|i Department of Biomedical Engineering , Seoul National University Hospital , Seoul , Republic of Korea .
authors.forename: Hee Chan
authors.initials: HC
authors.lastname: Kim
authors.affiliation: j Department of Pathology , Asan Medical Center, University of Ulsan College of Medicine , Seoul , Republic of Korea , and.
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: f Department of Obstetrics and Gynecology , Seoul National University Bundang Hospital , Gyeonggi-do , Republic of Korea .
authors.forename: Joon-Seok
authors.initials: JS
authors.lastname: Hong
authors.affiliation: k Department of Bioengineering , University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Huh
mesh_terms: D057005:Bioengineering / Q000379:methods; D001692:Biological Transport; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005947:Glucose / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D010920:Placenta / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*
chemical_list: D005947:Glucose
keywords: Glucose transfer; microfluidics; organ-on-a-chip; placenta in vitro model; placental barrier