title: Long-term maintenance of a microfluidic 3D human liver sinusoid.
abstract: The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip, using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic) and urea excretion (detoxification) were observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies.
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts.
authors.forename: Ljupcho
authors.initials: L
authors.lastname: Prodanov
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts.
authors.forename: Rohit
authors.initials: R
authors.lastname: Jindal
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts.
authors.forename: Shyam Sundhar
authors.initials: SS
authors.lastname: Bale
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts.
authors.forename: Manjunath
authors.initials: M
authors.lastname: Hegde
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts.
authors.forename: William J
authors.initials: WJ
authors.lastname: McCarty
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts.
authors.forename: Inna
authors.initials: I
authors.lastname: Golberg
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Bhushan
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts. ireis@sbi.org.|Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd., Piscataway, 08854, New Jersey. ireis@sbi.org.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts. berkusta@gmail.com.
authors.forename: Osman Berk
authors.initials: OB
authors.lastname: Usta
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008099:Liver / Q000502:physiology*; D044085:Microfluidics / Q000379:methods*; D008954:Models, Biological; D009924:Organ Culture Techniques / Q000379:methods*; D013997:Time Factors
keywords: 3D microtissue; hepatocytes; liver sinusoid; liver-on-a-chip; microfludics