The controlled presentation of TGF-beta1 to hepatocytes in a 3D-microfluidic cell culture system.
3D-microfluidic cell culture systems (3D-microFCCSs) support hepatocyte functions in vitro which can be further enhanced by controlled presentation of 100-200 pg/ml TGF-beta1, thus mimicking the roles of supporting cells in co-cultures. Controlled presentation of TGF-beta1 is achieved by either direct perfusion or in situ controlled release from gelatin microspheres immobilized in the 3D-microFCCS. Primary hepatocytes cultured for 7 days with the in situ controlled released TGF-beta1 exhibited up to four-fold higher albumin secretion and two-fold higher phase I/II enzymatic activities, significantly improving the sensitivity of hepatocytes to acetaminophen-mediated hepatotoxicity, compared to hepatocytes cultured with directly perfused TGF-beta1 or without TGF-beta1. The controlled presentation of TGF-beta1 enhanced hepatocyte functions in microfluidic systems without the complications of co-cultures, allowing for simplifications in drug testing and other hepatocyte-based applications.
Zhang
Chi
C
Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.
Chia
Ser-Mien
SM
Ong
Siew-Min
SM
Zhang
Shufang
S
Toh
Yi-Chin
YC
van Noort
Danny
D
Yu
Hanry
H
D000082:Acetaminophen / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005780:Gelatin / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D044085:Microfluidics / Q000379:methods*; D018625:Microscopy, Atomic Force; D008863:Microspheres; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000737:chemistry / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D053773:Transforming Growth Factor beta1; D000082:Acetaminophen; D005780:Gelatin