Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments

Adv Drug Deliv Rev. 2014 Apr;69-70:1-18. doi: 10.1016/j.addr.2014.02.008. Epub 2014 Mar 5.

Abstract

Drug failure due to toxicity indicators remains among the primary reasons for staggering drug attrition rates during clinical studies and post-marketing surveillance. Broader validation and use of next-generation 3-D improved cell culture models are expected to improve predictive power and effectiveness of drug toxicological predictions. However, after decades of promising research significant gaps remain in our collective ability to extract quality human toxicity information from in vitro data using 3-D cell and tissue models. Issues, challenges and future directions for the field to improve drug assay predictive power and reliability of 3-D models are reviewed.

Keywords: 3-D organoid culture; Cell culture models; Cellular microenvironment; Drug development; HTS screens; Nanotoxicity; Reasons for failure; Toxicity.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Culture Techniques / methods
  • Cell Culture Techniques / standards*
  • Cell Culture Techniques / trends
  • Drug-Related Side Effects and Adverse Reactions* / diagnosis
  • Drug-Related Side Effects and Adverse Reactions* / prevention & control
  • High-Throughput Screening Assays / methods
  • High-Throughput Screening Assays / standards*
  • High-Throughput Screening Assays / trends
  • Humans
  • Organoids / drug effects*
  • Organoids / physiology
  • Pharmaceutical Preparations / analysis
  • Toxicity Tests / methods
  • Toxicity Tests / standards
  • Toxicity Tests / trends

Substances

  • Pharmaceutical Preparations