Organotypic systems in drug metabolism and toxicity: challenges and opportunities
被引:16
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作者:
Dash, Ajit
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HemoShear LLC, Liver Surrogate Syst, Charlottesville, VA 22903 USA
Univ Virginia, Dept Surg, Charlottesville, VA USAHemoShear LLC, Liver Surrogate Syst, Charlottesville, VA 22903 USA
Dash, Ajit
[1
,2
]
Blackman, Brett R.
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机构:
Univ Virginia, Dept Med, Charlottesville, VA USA
Univ Virginia, Dept Biomed Engn, Charlottesville, VA USAHemoShear LLC, Liver Surrogate Syst, Charlottesville, VA 22903 USA
Blackman, Brett R.
[3
,4
]
Wamhoff, Brian R.
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机构:
Univ Virginia, Dept Surg, Charlottesville, VA USA
Univ Virginia, Dept Med, Charlottesville, VA USAHemoShear LLC, Liver Surrogate Syst, Charlottesville, VA 22903 USA
Wamhoff, Brian R.
[2
,3
]
机构:
[1] HemoShear LLC, Liver Surrogate Syst, Charlottesville, VA 22903 USA
[2] Univ Virginia, Dept Surg, Charlottesville, VA USA
[3] Univ Virginia, Dept Med, Charlottesville, VA USA
[4] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA
Introduction: The frequent failure of high-throughput screening cell-based tools to accurately predict in vivo responses, coupled with limitations of animal models in predicting human safety or drug efficacy, impairs the de-risking process for biotechnology/pharmaceutical companies as they make important decisions to enter human clinical trials. Organotypic systems strive to fill the gap between these screening and in vivo studies and provide a solution. Areas covered: The authors examine the various approaches to recreate physiological response on the bench and trace the evolution of organotypic systems, while discussing intrinsic challenges and opportunities that lie ahead. Furthermore, they cite literature that is the foundation of several biotechnology research companies addressing this issue and discuss major government-funded initiatives to aid the development of these systems in an effort to fill this existing gap. Expert opinion: Decisions from translational systems that bridge basic drug efficacy and toxicity with clinical outcome must be benchmarked against human-relevant endpoints and clinical data for early meaningful pre-clinical decisions. The use of human primary cells coupled with emerging technologies that allow precise control of the culture environment and analysis of meaningful endpoints paves the way for human organotypic systems as a major initiative in de-risking the drug discovery and development process.
机构:
Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden
Shen, Joanne X.
Youhanna, Sonia
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Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden
Youhanna, Sonia
Shafagh, Reza Zandi
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机构:
Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden
KTH Royal Inst Technol, Div Micro & Nanosyst, Stockholm, SwedenKarolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden
Shafagh, Reza Zandi
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Kele, Julianna
Lauschke, Volker M.
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Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, SwedenKarolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden
机构:
China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Zhang, Li'ao
Hu, Wenjun
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机构:
China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Hu, Wenjun
Qiu, Zhixia
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China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Qiu, Zhixia
Li, Zhiyu
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China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Li, Zhiyu
Bian, Jinlei
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China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Sch Pharm, Dept Med Chem, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
机构:
Rockefeller Univ, Lab Metab Regulat & Genet, New York, NY 10065 USARockefeller Univ, Lab Metab Regulat & Genet, New York, NY 10065 USA
Birsoy, Kivanc
Chandel, Navdeep S.
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机构:
Northwestern Univ, Dept Med & Biochem, Evanston, IL USA
Northwestern Univ, Dept Mol Genet, Evanston, IL USARockefeller Univ, Lab Metab Regulat & Genet, New York, NY 10065 USA
Chandel, Navdeep S.
Fendt, Sarah-Maria
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机构:
Vlaams Inst Biotechnol, Lab Cellular Metab & Metab Regulat, Flanders, Belgium
Katholieke Univ Leuven, Leuven, Belgium
Leuven Canc Inst, Leuven, BelgiumRockefeller Univ, Lab Metab Regulat & Genet, New York, NY 10065 USA
Fendt, Sarah-Maria
Green, Douglas R.
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机构:
St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USARockefeller Univ, Lab Metab Regulat & Genet, New York, NY 10065 USA
Green, Douglas R.
Li, Xiaoling
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机构:
Natl Inst Environm Hlth Sci, Signal Transduct Lab, Res Triangle Pk, NC USARockefeller Univ, Lab Metab Regulat & Genet, New York, NY 10065 USA
Li, Xiaoling
Muoio, Deborah M.
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Duke Mol Physiol Inst, Durham, NC USARockefeller Univ, Lab Metab Regulat & Genet, New York, NY 10065 USA