TABLE 1.
Role of ECM in in vitro models of renal function and disease.
| 2D models | |||||
|---|---|---|---|---|---|
| Culture architecture | ECM surrogate | Cells | Biological structure | Application | References |
| Coated PS plates | Fibronectin, laminin, collagen type IV and Matrigel | hESCs | Differentiated PT-like cells monolayer | Induced Differentiation to PT | Narayanan et al. (2013) |
| Coated glass plates and electrospun PCL-BU membranes | PCL-BU vs Collagens, laminin, MG, L-Dopa | HK-2, RPTEC | Differentiated PT-like cells monolayer | Synthetic membrane for BAK | van Gaal et al. (2021) |
| Coated PES/PVP/PSF-FC membranes | Collagen I, collagen IV, Laminin, L-DOPA | HPTCs, HK-2 | Differentiated PT-like cells monolayer | Synthetic membrane for BAK | Ni et al. (2011) |
| Coated PS- and PES-microstructured substrates | L-DOPA, collagen IV | ciPTEC | Monolayer of differentiated PT-like cells | Synthetic membrane for BAK | Hulshof et al. (2018) |
| Coated microPES hollow fiber membrane | L-DOPA, collagen IV | ciPTEC | Monolayer of differentiated PT-like cells | Synthetic membrane for BAK | Jansen et al. (2015) |
| Coated PE and PES-50 transwell membrane | L-DOPA, collagen IV | ciPTEC | Monolayer of differentiated PT-like cells | Synthetic membrane for BAK | Schophuizen et al. (2015) |
| Hydrogel bioprinted onto polyester Transwell membrane | Organovo’s NovoGel Bio-Ink | RPTEC Renal fibroblasts and HUVEC | RPTEC monolayer on top of hydrogel with HUVEC and fibroblasts | Differentiation CTX Fibrosis | King et al. (2017) |
| Coated Polycarbonate porous membrane within a microchip | Matrigel | RPTECs | Monolayer of differentiated PT-like cells | Synthetic membrane for BAK | Gao et al. (2011) |
| 2.5D Models | |||||
| Culture architecture | ECM surrogate | Cells | Biological structure | Application | References |
| Coated Micropatterned Silicon-PDMS surfaces | Fibronectin, laminin, matrigel. Matrigel in medium | MDCK, RPTEC, LLC-PK1 | Cysts and tubules (PT) | Morphogenesis Nephrotoxicity | Bosch-Fortea et al. (2019) |
| Hydrogels Coated PS plates | Matrigel | HPTCs | Tubules (PT) | Morphogenesis | Zhang et al. (2011) |
| 3D Models | |||||
| Culture architecture | ECM surrogate | Cells | Biological structure | Application | References |
| Hydrogel | 20% Growth factor-depleted Matrigel 80%Collagen I | Mouse embryonic UB and BSN primary cells mIMCD3 | Cysts and tubules (UB) | Tubulogenesis Development | Sakurai et al. (1997) |
| Hydrogel | Matrigel | Primary baby mouse kidney epithelial cells | Tubules | Tubulogenesis | Taub et al. (1990) |
| Hydrogel | Rat tail collagen type I | Primary murine renal cells | Tubule- and glomerulus-like structures | Morphogenesis | Joraku et al. (2009) |
| 0.4 µm Polyester Transwell membranes | Matrigel and collagen I (1:1) | RPTEC | Tubules (PT) | Tubulogenesis | Miya et al. (2011) |
| 0.4 µm polycarbonate Transwell membranes | Matrigel and rat tail collagen I (1:1) | NKi-2 | Tubules | Morphogenesis Nephrotoxicity | DesRochers et al. (2013) |
| Hydrogel | Collagen | MDCK co-cultured with Swiss 3T3 | Tubules (Distal nephron) | Morphogenesis | Montesano et al. (1991a) |
| Hydrogel | Collagen | MDCK and co-cultured with MRC-5 | Tubules (Distal nephron) | Morphogenesis | Montesano et al. (1991b) |
| Hydrogel | Collagen | HK-2 | Tubules (PT) | Morphogenesis | Kher et al. (2011) |
| Hydrogel | Matrigel | Mouse renal tubule fragments | Cysts and tubules (Collecting Duct) | Genetic disease (ADPKD) | Dixon et al. (2020) |
| Hydrogel | Growth factor reduced, phenol red-free Matrigel | RPTEC/TERT1 | Tubules (PT) | Nephrotoxicity | Secker et al. (2018) |
| Casting molds in 12-well plate | Collagen-Matrigel | Neonatal rat renal cells | Tubule- and glomerulus-like structures | Morphogenesis | Lü et al. (2012) |
| Round bottom microwell plate | GFR-Matrigel | MDCK | Tubules (distal nephron) | Morphogenesis | Hirashima et al. (2017) |
| Hydrogel | Collagen I, GRF-Matrigel | RPTEC, renal fibroblasts and HUVEC | Tubules (PT) and endothelial unit | Tubulo-vascular interactions | Wang et al. (2020) |
| Printed silicon gasket | Gelatin, Fibrinogen | PTECT-TERT1, GMECs | Tubules (PT) and endothelial unit | Epithelial transport Tubulo-vascular interactions | Lin et al. (2019) |
| Hydrogel | Collagen I | HKC-8 and WS-1 | HKC-8 monolayer on top of WS-1 embeded hydrogel | Fibrosis Nephrotoxicity | Moll et al. (2013) |
| Polystyrene multiwell plate | Covalent polymer networks of heparin and/or starPEG | HK-2 | Tubules (PT) | Tubulogenesis | Weber et al. (2017) |
| PEGDA Hydrogel | HA | Mouse proximal tubule cells | Tubules (PT) | Nephrotoxicity | Astashkina et al. (2012); Astashkina et al. (2014) |
| Hydrogel | HA Matrigel | Embryonic rat UB | Tubules (UB) | Morphogenesis | Rosines et al. (2007) |
| PEG hydrogel | PEG functionalized with RGD peptide, laminin-1 | MDCK | Cysts | Epithelial morphogenesis | Chung et al. (2008) |
| Scaffold | Silk | hiPSCs | Organoids | Development Differentiation | Gupta et al. (2019) |
| Scaffold | Thiol-ene crosslinked alginate | hiPSCs | Organoids | Development Differentiation | Geuens et al. (2021); Ruiter et al. (2022) |
| Scaffold | PLA Matrigel-Geltrex | HRECs | Monolayer- | ECM biomechanical properties | Love et al. (2019) |
| Hydrogel | PEG-4-MAL | MDCK | Cysts | ECM biomechanical properties | Enemchukwu et al. (2016) |
| PCLdi (u-UPy) electro-spun HFM | Collagen I, IV, fibronectin, laminin | hRPTECs | Monolayer | Bioactive membranes for BAKs | Dankers et al. (2011) |
| Electrospun transwell membrane | 1:1 dKECM-PLC | hRPCs HUVEC | Monolayer | Differentiation Tubule-Vascular unit Nephrotoxicity | Sobreiro-Almeida et al. (2019); Sobreiro-Almeida et al. (2020) |
| Melt-electrowritten tubular scaffold | PCL | ciPTEC HUVEC | Monolayer Self-produced ECM | Tubule-Vascular unit Bioactive membranes for BAKs | van Genderen et al. (2021) |
| Silk-based porous scaffold | Matrigel and Collagen-Matrigel | MEK | Tubules and cysts | Genetic disease (ADPKD) | Subramanian et al. (2010) |
| Silk-based porous scaffold | Collagen type I and Matrigel (1:1) | mIMCD | Cysts | Genetic disease (ADPKD) | Subramanian et al. (2012) |
| Hollow tubes insidehydrogel | Collagen I | MDCK Primary PCT from transgenic mice | Tubules | Genetic disease (ADPKD) | Myram et al. (2021) |
| Extruded topographic hollow fiber (h- FIBER) | RGD-conjugated alginate | Podocytes and endothelial cells | Tubules Glomerulus-like structure | Glomerular filtration studies | Xie et al. (2020) |
| EDC hollow fibers | Collagen IV | HK-2 | Tubules (PT) | Bioengineering renal tubules | Shen et al. (2015) |
| MicroPES HFM | Collagen IV and L-DOPA | ciPTEC | Tubules (PT) | Bioactive membranes for BAKs | Chevtchik et al. (2016) |
| PCL tubular nanofiber scaffold | Collagen IV and L-DOPA | ciPTEC-OAT1 | Tubules (PT) | Bioactive membranes for BAKs Nephrotoxicity | Jansen et al. (2019) |
| Bioprinted Scaffolds | |||||
| Culture architecture | ECM surrogate | Cells | Biological structure | Application | References |
| Bioprinted renal constructs | dKECMMA | Human primary kidney cells | Tubular Glomerular-like structures | Tissue bioengineering | Ali et al. (2019) |
| Bioprinted renal construct | dKECM Gelatin | hRPCs HUVEC, podocytes | 3D glomerular model | Regenerative medicine | Sobreiro-Almeida et al. (2021) |
| Bioprinted hollow tubules | dECM and alginate | RPTEC, HUVEC, hBMMSCs | Perfused Tubules and capillaries | Regenerative medicine | Singh et al. (2020) |
| Bioprinted hollow tubules | Gelatin-fibrin hydrogel | RPTEC/TERT1, GMECs | Perfused Tubules and capillaries | Tubule-Vascular unit Nephrotoxicity | Homan et al. (2016); Lin et al. (2019); Aceves et al. (2022) |
| Hydrogel-sandwiched, bioprinted tubular structure | Collagen I, Matrigel, Fibrin | RPTEC/TERT1, iRECs | Perfused Tubules | Bioengineering renal tubules | Tröndle et al. (2021) |
Natural polymers: HA: hyaluronic acid, FMB: fibrin microbreads, dKECMMA: photo-crosslinable kidney ECM-derived bioink.
Synthetic polymers: EDC: 1-ethyl-3-(3- (dimethylamino)propyl) carbodiimide hydrochloride, PA: polyacrylamide.
Cell lines: HUTECs: Primary human tubular epithelial cells, HK-2: Human kidney-2, HPTCs: Human primary renal proximal tubule cells, RPTECs: renal proximal tubular epithelial cells, hESCs: embryonic stem cells, HUVEC: human umbilical vein endothelial cells, NKi-2: human renal epithelial cells, MDCK: Madin-Darby canine kidney, MRC-5: human fibroblasts, MEK: mouse embryonic kidney, HK-2: human immortalized proximal tubule epithelial cells, ciPTECs: Conditionally immortalized proximal tubule epithelial cells, HRECs: Human renal epithelial cells, LLC-PK1: pig kidney epithelial cells, 3T3: fibroblasts, UB: ureteric bud,HEK-293: Human embryonic kidney cell line, CaKi-1: human renal cancer cells, mIMCD: mouse inner medullary collecting duct, GMECs: glomerular microvascular endothelial cells, HKC-8: human proximal tubular epithelial cells, WS-1: human dermal fibroblasts, hBMMSCs: human bone marrow-derived mesenchymal stem cells, GMECs: glomerular microvascular endothelial cells, iRECs: induced renal tubular epithelial cells.