title: Enhancement of renal epithelial cell functions through microfluidic-based coculture with adipose-derived stem cells.
abstract: Current hemodialysis has functional limitations and is insufficient for renal transplantation. The bioartificial tubule device has been developed to contribute to metabolic functions by implanting renal epithelial cells into hollow tubes and showed a higher survival rate in acute kidney injury patients. In healthy kidney, epithelial cells are surrounded by various types of cells that interact with extracellular matrices, which are primarily composed of laminin and collagen. The current study developed a microfluidic coculture platform to enhance epithelial cell function in bioartificial microenvironments with multiple microfluidic channels that are microfabricated by polydimethylsiloxane. Collagen gel (CG) encapsulated with adipose-derived stem cells (CG-ASC) was injected into a central microfluidic channel for three-dimensional (3D) culture. The resuspended Madin-Darby canine kidney (MDCK) cells were injected into nascent channels and formed an epithelial monolayer. In comparison to coculture different cells using the commercial transwell system, the current coculture device allowed living cell monitoring of both the MDCK epithelial monolayer and CG-ASC in a 3D microenvironment. By coculture with CG-ASC, the cell height was increased with columnar shapes in MDCK. Promotion of cilia formation and functional expression of the ion transport protein in MDCK were also observed in the cocultured microfluidic device. When applying fluid flow, the intracellular protein dynamics can be monitored in the current platform by using the time-lapse confocal microscopy and transfection of GFP-tubulin plasmid in MDCK. Thus, this microfluidic coculture device provides the renal epithelial cells with both morphological and functional improvements that may avail to develop bioartificial renal chips.
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Chang
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Chen
authors.forename: Hans I-Chen
authors.initials: HI
authors.lastname: Harn
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tang
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Wu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000166:cytology*; D044085:Microfluidics / Q000379:methods*; D051381:Rats; D013234:Stem Cells / Q000166:cytology*
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5722-6
references.pmid: 17389399
references.citation: Nat Rev Mol Cell Biol. 2008 Nov;9(11):887-901
references.pmid: 18946477
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1254-9
references.pmid: 17229844
references.citation: Science. 1999 Apr 2;284(5411):143-7
references.pmid: 10102814
references.citation: Lab Chip. 2005 May;5(5):553-9
references.pmid: 15856094
references.citation: Histochem Cell Biol. 2008 Jun;129(6):687-93
references.pmid: 18365235
references.citation: Curr Opin Nephrol Hypertens. 2008 Jan;17(1):25-31
references.pmid: 18090666
references.citation: Anal Chem. 2008 May 15;80(10):3640-7
references.pmid: 18393530
references.citation: Kidney Int. 2010 Jul;78(1):60-8
references.pmid: 20336056
references.citation: Kidney Int. 1999 Jun;55(6):2502-14
references.pmid: 10354300
references.citation: Biotechnol Prog. 2012 Mar-Apr;28(2):474-84
references.pmid: 22095740
references.citation: Annu Rev Physiol. 2009;71:83-113
references.pmid: 19572811
references.citation: Lab Chip. 2010 Jan 7;10(1):36-42
references.pmid: 20024048
references.citation: Am J Physiol Renal Physiol. 2003 Sep;285(3):F388-96
references.pmid: 12890662
references.citation: Nat Rev Mol Cell Biol. 2006 Mar;7(3):211-24
references.pmid: 16496023
references.citation: Integr Biol (Camb). 2011 Feb;3(2):134-41
references.pmid: 21079870
references.citation: Am J Physiol Cell Physiol. 2006 Apr;290(4):C947-9
references.pmid: 16531571
references.citation: Nat Biotechnol. 1999 May;17(5):451-5
references.pmid: 10331803
references.citation: Stem Cells. 2010 Mar 31;28(3):573-84
references.pmid: 20099318
references.citation: Traffic. 2004 Jan;5(1):1-9
references.pmid: 14675420
references.citation: Tissue Eng. 2001 Apr;7(2):211-28
references.pmid: 11304456
references.citation: J Biomech. 2008;41(4):813-21
references.pmid: 18190919
references.citation: Am J Physiol Renal Physiol. 2000 Aug;279(2):F270-4
references.pmid: 10919845
references.citation: Nat Biotechnol. 2008 Jan;26(1):120-6
references.pmid: 18026090
references.citation: Biomaterials. 2006 May;27(14):2890-7
references.pmid: 16439014
references.citation: Hemodial Int. 2011 Apr;15(2):183-92
references.pmid: 21395969
references.citation: Lab Chip. 2009 Jan 21;9(2):269-75
references.pmid: 19107284
references.citation: Circ Res. 2007 May 11;100(9):1249-60
references.pmid: 17495232
references.citation: Kidney Int. 2006 Jun;69(11):2029-36
references.pmid: 16732193
references.citation: Am J Physiol Renal Physiol. 2006 Jun;290(6):F1320-8
references.pmid: 16396941
references.citation: Lancet. 2003 Mar 1;361(9359):774-6
references.pmid: 12620752
references.citation: Nat Rev Mol Cell Biol. 2009 May;10(5):344-52
references.pmid: 19339978
references.citation: Lab Chip. 2012 Jun 21;12(12):2156-64
references.pmid: 22555377
references.citation: Lab Chip. 2011 Jan 21;11(2):191-3
references.pmid: 21152593
references.citation: Mol Biol Cell. 2002 Dec;13(12):4279-95
references.pmid: 12475952
references.citation: Biomaterials. 2003 Jun;24(13):2267-75
references.pmid: 12699663
references.citation: Cell Tissue Res. 2007 Mar;327(3):449-62
references.pmid: 17053900
references.citation: FASEB J. 1999 Nov;13(14):1883-900
references.pmid: 10544172
references.citation: Lab Chip. 2010 Jan 21;10(2):235-9
references.pmid: 20066252
references.citation: Am J Physiol Cell Physiol. 2009 Jan;296(1):C13-24
references.pmid: 19064501
references.citation: Biochem Biophys Res Commun. 2005 Apr 1;329(1):256-65
references.pmid: 15721301
references.citation: Kidney Int. 2000 Apr;57(4):1539-48
references.pmid: 10760089
references.citation: Stem Cells. 2007 Mar;25(3):750-60
references.pmid: 17095706
references.citation: Nephrol Dial Transplant. 2010 Dec;25(12):3990-5
references.pmid: 20543211
references.citation: Int J Exp Pathol. 2000 Jun;81(3):173-82
references.pmid: 10971738
references.citation: Crit Rev Oncol Hematol. 2000 Nov-Dec;36(2-3):59-60
references.pmid: 11033296
references.citation: Nephron. 2002 Aug;91(4):688-94
references.pmid: 12138274
references.citation: Lab Chip. 2005 Jan;5(1):111-8
references.pmid: 15616749
references.citation: Science. 2010 Jun 25;328(5986):1662-8
references.pmid: 20576885