Development of a living membrane comprising of a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane

C.M.S. Schophuizen, Ilaria De Napoli, J. Jansen, Sandra Da Silva Teixeira, M. Wilmer, J.G. Hoenderop, L.P.W. van den Heuvel, R. Masereeuw, Dimitrios Stamatialis

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Abstract

The need for improved renal replacement therapies has stimulated innovative research for the development of a cell-based renal assist device. A key requirement for such a device is the formation of a “living membrane”, consisting of a tight kidney cell monolayer with preserved functional organic ion transporters on a suitable artificial membrane surface. In this work, we applied a unique conditionally immortalized proximal tubule epithelial cell (ciPTEC) line with an optimized coating strategy on polyethersulfone (PES) membranes to develop a living membrane with a functional proximal tubule epithelial cell layer. PES membranes were coated with combinations of 3,4-dihydroxy-l-phenylalanine and human collagen IV (Coll IV). The optimal coating time and concentrations were determined to achieve retention of vital blood components while preserving high water transport and optimal ciPTEC adhesion. The ciPTEC monolayers obtained were examined through immunocytochemistry to detect zona occludens 1 tight junction proteins. Reproducible monolayers were formed when using a combination of 2 mg ml−1 3,4-dihydroxy-l-phenylalanine (4 min coating, 1 h dissolution) and 25 μg ml−1 Coll IV (4 min coating). The successful transport of 14C-creatinine through the developed living membrane system was used as an indication for organic cation transporter functionality. The addition of metformin or cimetidine significantly reduced the creatinine transepithelial flux, indicating active creatinine uptake in ciPTECs, most likely mediated by the organic cation transporter, OCT2 (SLC22A2). In conclusion, this study shows the successful development of a living membrane consisting of a reproducible ciPTEC monolayer on PES membranes, an important step towards the development of a bioartificial kidney.
Original languageEnglish
Pages (from-to)22-32
JournalActa biomaterialia
Volume14
DOIs
Publication statusPublished - 2015

Fingerprint

Polymeric membranes
Proximal Kidney Tubule
Monolayers
Membranes
Epithelial Cells
Creatinine
Coatings
Phenylalanine
Kidney
Cations
Collagen
Zonula Occludens-1 Protein
Artificial Membranes
Positive ions
Equipment and Supplies
Renal Replacement Therapy
Metformin
Cimetidine
Herpes Zoster
polyether sulfone

Keywords

  • METIS-314305
  • IR-99862

Cite this

Schophuizen, C.M.S. ; De Napoli, Ilaria ; Jansen, J. ; Da Silva Teixeira, Sandra ; Wilmer, M. ; Hoenderop, J.G. ; van den Heuvel, L.P.W. ; Masereeuw, R. ; Stamatialis, Dimitrios. / Development of a living membrane comprising of a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane. In: Acta biomaterialia. 2015 ; Vol. 14. pp. 22-32.
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abstract = "The need for improved renal replacement therapies has stimulated innovative research for the development of a cell-based renal assist device. A key requirement for such a device is the formation of a “living membrane”, consisting of a tight kidney cell monolayer with preserved functional organic ion transporters on a suitable artificial membrane surface. In this work, we applied a unique conditionally immortalized proximal tubule epithelial cell (ciPTEC) line with an optimized coating strategy on polyethersulfone (PES) membranes to develop a living membrane with a functional proximal tubule epithelial cell layer. PES membranes were coated with combinations of 3,4-dihydroxy-l-phenylalanine and human collagen IV (Coll IV). The optimal coating time and concentrations were determined to achieve retention of vital blood components while preserving high water transport and optimal ciPTEC adhesion. The ciPTEC monolayers obtained were examined through immunocytochemistry to detect zona occludens 1 tight junction proteins. Reproducible monolayers were formed when using a combination of 2 mg ml−1 3,4-dihydroxy-l-phenylalanine (4 min coating, 1 h dissolution) and 25 μg ml−1 Coll IV (4 min coating). The successful transport of 14C-creatinine through the developed living membrane system was used as an indication for organic cation transporter functionality. The addition of metformin or cimetidine significantly reduced the creatinine transepithelial flux, indicating active creatinine uptake in ciPTECs, most likely mediated by the organic cation transporter, OCT2 (SLC22A2). In conclusion, this study shows the successful development of a living membrane consisting of a reproducible ciPTEC monolayer on PES membranes, an important step towards the development of a bioartificial kidney.",
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author = "C.M.S. Schophuizen and {De Napoli}, Ilaria and J. Jansen and {Da Silva Teixeira}, Sandra and M. Wilmer and J.G. Hoenderop and {van den Heuvel}, L.P.W. and R. Masereeuw and Dimitrios Stamatialis",
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Schophuizen, CMS, De Napoli, I, Jansen, J, Da Silva Teixeira, S, Wilmer, M, Hoenderop, JG, van den Heuvel, LPW, Masereeuw, R & Stamatialis, D 2015, 'Development of a living membrane comprising of a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane' Acta biomaterialia, vol. 14, pp. 22-32. https://doi.org/10.1016/j.actbio.2014.12.002

Development of a living membrane comprising of a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane. / Schophuizen, C.M.S.; De Napoli, Ilaria; Jansen, J.; Da Silva Teixeira, Sandra; Wilmer, M.; Hoenderop, J.G.; van den Heuvel, L.P.W.; Masereeuw, R.; Stamatialis, Dimitrios.

In: Acta biomaterialia, Vol. 14, 2015, p. 22-32.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Development of a living membrane comprising of a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane

AU - Schophuizen, C.M.S.

AU - De Napoli, Ilaria

AU - Jansen, J.

AU - Da Silva Teixeira, Sandra

AU - Wilmer, M.

AU - Hoenderop, J.G.

AU - van den Heuvel, L.P.W.

AU - Masereeuw, R.

AU - Stamatialis, Dimitrios

PY - 2015

Y1 - 2015

N2 - The need for improved renal replacement therapies has stimulated innovative research for the development of a cell-based renal assist device. A key requirement for such a device is the formation of a “living membrane”, consisting of a tight kidney cell monolayer with preserved functional organic ion transporters on a suitable artificial membrane surface. In this work, we applied a unique conditionally immortalized proximal tubule epithelial cell (ciPTEC) line with an optimized coating strategy on polyethersulfone (PES) membranes to develop a living membrane with a functional proximal tubule epithelial cell layer. PES membranes were coated with combinations of 3,4-dihydroxy-l-phenylalanine and human collagen IV (Coll IV). The optimal coating time and concentrations were determined to achieve retention of vital blood components while preserving high water transport and optimal ciPTEC adhesion. The ciPTEC monolayers obtained were examined through immunocytochemistry to detect zona occludens 1 tight junction proteins. Reproducible monolayers were formed when using a combination of 2 mg ml−1 3,4-dihydroxy-l-phenylalanine (4 min coating, 1 h dissolution) and 25 μg ml−1 Coll IV (4 min coating). The successful transport of 14C-creatinine through the developed living membrane system was used as an indication for organic cation transporter functionality. The addition of metformin or cimetidine significantly reduced the creatinine transepithelial flux, indicating active creatinine uptake in ciPTECs, most likely mediated by the organic cation transporter, OCT2 (SLC22A2). In conclusion, this study shows the successful development of a living membrane consisting of a reproducible ciPTEC monolayer on PES membranes, an important step towards the development of a bioartificial kidney.

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KW - METIS-314305

KW - IR-99862

U2 - 10.1016/j.actbio.2014.12.002

DO - 10.1016/j.actbio.2014.12.002

M3 - Article

VL - 14

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EP - 32

JO - Acta biomaterialia

JF - Acta biomaterialia

SN - 1742-7061

ER -