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Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy

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Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy. / Baker, Simon C; Shabir, Saqib; Southgate, Jennifer.

In: MOLECULAR PHARMACEUTICS, Vol. 11, No. 7, 07.07.2014, p. 1964-70.

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Harvard

Baker, SC, Shabir, S & Southgate, J 2014, 'Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy', MOLECULAR PHARMACEUTICS, vol. 11, no. 7, pp. 1964-70. https://doi.org/10.1021/mp500065m

APA

Baker, S. C., Shabir, S., & Southgate, J. (2014). Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy. MOLECULAR PHARMACEUTICS, 11(7), 1964-70. https://doi.org/10.1021/mp500065m

Vancouver

Baker SC, Shabir S, Southgate J. Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy. MOLECULAR PHARMACEUTICS. 2014 Jul 7;11(7):1964-70. https://doi.org/10.1021/mp500065m

Author

Baker, Simon C ; Shabir, Saqib ; Southgate, Jennifer. / Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy. In: MOLECULAR PHARMACEUTICS. 2014 ; Vol. 11, No. 7. pp. 1964-70.

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@article{bf09c14341cd4e56a5cf8782b1a18a53,
title = "Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy",
abstract = "The bladder is an important tissue in which to evaluate xenobiotic drug interactions and toxicities due to the concentration of parent drug and hepatic/enteric-derived metabolites in the urine as a result of renal excretion. Breaching of the barrier provided by the bladder epithelial lining (the urothelium) can expose the underlying tissues to urine and cause harmful effects (e.g., cystitis or cancer). Human urothelium is most commonly represented in vitro as immortalized or established cancer-derived cell lines, but the compromised ability of such cells to undergo differentiation and barrier formation means that nonimmortalized, normal human urothelial (NHU) cells provide a more relevant cell culture system. The impressive capacity for urothelial self-renewal in vivo can be harnessed in vitro to generate experimentally-useful quantities of NHU cells, which can subsequently be differentiated to form a functional or {"}biomimetic{"} urothelium. When seeded onto permeable membranes, these barrier-forming human urothelial tissue models enable the modeling of serum and luminal (intravesical) exposure to drugs and metabolites, thus supporting efficacy/toxicity assessments. Biomimetic human urothelial constructs provide a potential step along the preclinical trail and may support the extrapolation from rodent in vivo data to determine human relevance. Early evidence is beginning to demonstrate that human urothelium in vitro can provide information that supersedes conventional rodent studies, but further validation is needed to support widespread adoption.",
keywords = "urinary tract, Ureter, toxicology, pharmacology, drug delivery",
author = "Baker, {Simon C} and Saqib Shabir and Jennifer Southgate",
year = "2014",
month = jul,
day = "7",
doi = "10.1021/mp500065m",
language = "English",
volume = "11",
pages = "1964--70",
journal = "MOLECULAR PHARMACEUTICS",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "7",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy

AU - Baker, Simon C

AU - Shabir, Saqib

AU - Southgate, Jennifer

PY - 2014/7/7

Y1 - 2014/7/7

N2 - The bladder is an important tissue in which to evaluate xenobiotic drug interactions and toxicities due to the concentration of parent drug and hepatic/enteric-derived metabolites in the urine as a result of renal excretion. Breaching of the barrier provided by the bladder epithelial lining (the urothelium) can expose the underlying tissues to urine and cause harmful effects (e.g., cystitis or cancer). Human urothelium is most commonly represented in vitro as immortalized or established cancer-derived cell lines, but the compromised ability of such cells to undergo differentiation and barrier formation means that nonimmortalized, normal human urothelial (NHU) cells provide a more relevant cell culture system. The impressive capacity for urothelial self-renewal in vivo can be harnessed in vitro to generate experimentally-useful quantities of NHU cells, which can subsequently be differentiated to form a functional or "biomimetic" urothelium. When seeded onto permeable membranes, these barrier-forming human urothelial tissue models enable the modeling of serum and luminal (intravesical) exposure to drugs and metabolites, thus supporting efficacy/toxicity assessments. Biomimetic human urothelial constructs provide a potential step along the preclinical trail and may support the extrapolation from rodent in vivo data to determine human relevance. Early evidence is beginning to demonstrate that human urothelium in vitro can provide information that supersedes conventional rodent studies, but further validation is needed to support widespread adoption.

AB - The bladder is an important tissue in which to evaluate xenobiotic drug interactions and toxicities due to the concentration of parent drug and hepatic/enteric-derived metabolites in the urine as a result of renal excretion. Breaching of the barrier provided by the bladder epithelial lining (the urothelium) can expose the underlying tissues to urine and cause harmful effects (e.g., cystitis or cancer). Human urothelium is most commonly represented in vitro as immortalized or established cancer-derived cell lines, but the compromised ability of such cells to undergo differentiation and barrier formation means that nonimmortalized, normal human urothelial (NHU) cells provide a more relevant cell culture system. The impressive capacity for urothelial self-renewal in vivo can be harnessed in vitro to generate experimentally-useful quantities of NHU cells, which can subsequently be differentiated to form a functional or "biomimetic" urothelium. When seeded onto permeable membranes, these barrier-forming human urothelial tissue models enable the modeling of serum and luminal (intravesical) exposure to drugs and metabolites, thus supporting efficacy/toxicity assessments. Biomimetic human urothelial constructs provide a potential step along the preclinical trail and may support the extrapolation from rodent in vivo data to determine human relevance. Early evidence is beginning to demonstrate that human urothelium in vitro can provide information that supersedes conventional rodent studies, but further validation is needed to support widespread adoption.

KW - urinary tract

KW - Ureter

KW - toxicology

KW - pharmacology

KW - drug delivery

U2 - 10.1021/mp500065m

DO - 10.1021/mp500065m

M3 - Article

C2 - 24697150

VL - 11

SP - 1964

EP - 1970

JO - MOLECULAR PHARMACEUTICS

JF - MOLECULAR PHARMACEUTICS

SN - 1543-8384

IS - 7

ER -