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Front Pharmacol. 2016 Sep 22;7:334. eCollection 2016.

Drug Discovery via Human-Derived Stem Cell Organoids.

Author information

1
Department of Neurosurgery, Xiangya Hospital, Central South UniversityChangsha, China; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, HoustonTX, USA.
2
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, HoustonTX, USA; Department of Psychiatry, The Second Xiangya Hospital, Central South University, ChangshaHunan, China; Mental Health Institute of the Second Xiangya Hospital, Central South University, ChangshaHunan, China; Chinese National Clinical Research Center on Mental Disorders, ChangshaHunan, China; Chinese National Technology Institute on Mental Disorders, ChangshaHunan, China; Hunan Key Laboratory of Psychiatry and Mental Health, ChangshaHunan, China.
3
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston TX, USA.
4
Department of Neurosurgery, Xiangya Hospital, Central South University Changsha, China.
5
Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen UniversityGuangzhou, China; Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen UniversityGuangzhou, China.

Abstract

Patient-derived cell lines and animal models have proven invaluable for the understanding of human intestinal diseases and for drug development although both inherently comprise disadvantages and caveats. Many genetically determined intestinal diseases occur in specific tissue microenvironments that are not adequately modeled by monolayer cell culture. Likewise, animal models incompletely recapitulate the complex pathologies of intestinal diseases of humans and fall short in predicting the effects of candidate drugs. Patient-derived stem cell organoids are new and effective models for the development of novel targeted therapies. With the use of intestinal organoids from patients with inherited diseases, the potency and toxicity of drug candidates can be evaluated better. Moreover, owing to the novel clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 genome-editing technologies, researchers can use organoids to precisely modulate human genetic status and identify pathogenesis-related genes of intestinal diseases. Therefore, here we discuss how patient-derived organoids should be grown and how advanced genome-editing tools may be applied to research on modeling of cancer and infectious diseases. We also highlight practical applications of organoids ranging from basic studies to drug screening and precision medicine.

KEYWORDS:

inflammatory bowel disease; intestinal cancer; organoid; pluripotent stem cells

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