Using miniature brain implants in rodents for novel drug discovery

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Introduction: There continues to be a need to create an artificial human blood-brain barrier for pharmacological testing and modeling of diseases. Our group has recently vascularized human brain organoids with human iPSC-derived endothelial cells. Other groups have achieved brain organoid perfusion after vascularization with murine endothelial cells. Areas covered: This review article discusses the remaining hurdles, advantages, and limitations of creating a human organoid blood-brain barrier in rodents for novel drug discovery. Expert opinion: The creation of a human organoid blood-brain barrier in rodents will be feasible with appropriate molecular and cellular cues. An artificial human blood-brain barrier model may be used for pharmacological testing or for the study of the human blood-brain barrier in development or disease. Potential limitations of the model include an inferior competence of the blood-brain organoid barrier, the immunodeficient environment and low reproducibility due to variations in organoid morphology and vascularization. Despite its limitations, an artificial human blood-brain barrier model in rodents will further our understanding of blood-brain barrier pharmacology, and the field is expected to see significant advances in the next years.

Original languageEnglish (US)
Pages (from-to)379-386
Number of pages8
JournalExpert Opinion on Drug Discovery
Volume14
Issue number4
DOIs
StatePublished - Apr 3 2019

Fingerprint

Organoids
Drug Discovery
Blood-Brain Barrier
Rodentia
Brain
Blood Substitutes
Pharmacology
Endothelial Cells
Expert Testimony
Mental Competency
Cues
Perfusion

Keywords

  • blood-brain barrier
  • Human brain organoid
  • human endothelial cells
  • induced pluripotent stem cells
  • perfusion
  • vascularization

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Using miniature brain implants in rodents for novel drug discovery. / Waldau, Ben.

In: Expert Opinion on Drug Discovery, Vol. 14, No. 4, 03.04.2019, p. 379-386.

Research output: Contribution to journalReview article

@article{e0516a6ea8874194a90e798c95f788cb,
title = "Using miniature brain implants in rodents for novel drug discovery",
abstract = "Introduction: There continues to be a need to create an artificial human blood-brain barrier for pharmacological testing and modeling of diseases. Our group has recently vascularized human brain organoids with human iPSC-derived endothelial cells. Other groups have achieved brain organoid perfusion after vascularization with murine endothelial cells. Areas covered: This review article discusses the remaining hurdles, advantages, and limitations of creating a human organoid blood-brain barrier in rodents for novel drug discovery. Expert opinion: The creation of a human organoid blood-brain barrier in rodents will be feasible with appropriate molecular and cellular cues. An artificial human blood-brain barrier model may be used for pharmacological testing or for the study of the human blood-brain barrier in development or disease. Potential limitations of the model include an inferior competence of the blood-brain organoid barrier, the immunodeficient environment and low reproducibility due to variations in organoid morphology and vascularization. Despite its limitations, an artificial human blood-brain barrier model in rodents will further our understanding of blood-brain barrier pharmacology, and the field is expected to see significant advances in the next years.",
keywords = "blood-brain barrier, Human brain organoid, human endothelial cells, induced pluripotent stem cells, perfusion, vascularization",
author = "Ben Waldau",
year = "2019",
month = "4",
day = "3",
doi = "10.1080/17460441.2019.1577816",
language = "English (US)",
volume = "14",
pages = "379--386",
journal = "Expert Opinion on Drug Discovery",
issn = "1746-0441",
publisher = "Informa Healthcare",
number = "4",

}

TY - JOUR

T1 - Using miniature brain implants in rodents for novel drug discovery

AU - Waldau, Ben

PY - 2019/4/3

Y1 - 2019/4/3

N2 - Introduction: There continues to be a need to create an artificial human blood-brain barrier for pharmacological testing and modeling of diseases. Our group has recently vascularized human brain organoids with human iPSC-derived endothelial cells. Other groups have achieved brain organoid perfusion after vascularization with murine endothelial cells. Areas covered: This review article discusses the remaining hurdles, advantages, and limitations of creating a human organoid blood-brain barrier in rodents for novel drug discovery. Expert opinion: The creation of a human organoid blood-brain barrier in rodents will be feasible with appropriate molecular and cellular cues. An artificial human blood-brain barrier model may be used for pharmacological testing or for the study of the human blood-brain barrier in development or disease. Potential limitations of the model include an inferior competence of the blood-brain organoid barrier, the immunodeficient environment and low reproducibility due to variations in organoid morphology and vascularization. Despite its limitations, an artificial human blood-brain barrier model in rodents will further our understanding of blood-brain barrier pharmacology, and the field is expected to see significant advances in the next years.

AB - Introduction: There continues to be a need to create an artificial human blood-brain barrier for pharmacological testing and modeling of diseases. Our group has recently vascularized human brain organoids with human iPSC-derived endothelial cells. Other groups have achieved brain organoid perfusion after vascularization with murine endothelial cells. Areas covered: This review article discusses the remaining hurdles, advantages, and limitations of creating a human organoid blood-brain barrier in rodents for novel drug discovery. Expert opinion: The creation of a human organoid blood-brain barrier in rodents will be feasible with appropriate molecular and cellular cues. An artificial human blood-brain barrier model may be used for pharmacological testing or for the study of the human blood-brain barrier in development or disease. Potential limitations of the model include an inferior competence of the blood-brain organoid barrier, the immunodeficient environment and low reproducibility due to variations in organoid morphology and vascularization. Despite its limitations, an artificial human blood-brain barrier model in rodents will further our understanding of blood-brain barrier pharmacology, and the field is expected to see significant advances in the next years.

KW - blood-brain barrier

KW - Human brain organoid

KW - human endothelial cells

KW - induced pluripotent stem cells

KW - perfusion

KW - vascularization

UR - http://www.scopus.com/inward/record.url?scp=85062993018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062993018&partnerID=8YFLogxK

U2 - 10.1080/17460441.2019.1577816

DO - 10.1080/17460441.2019.1577816

M3 - Review article

VL - 14

SP - 379

EP - 386

JO - Expert Opinion on Drug Discovery

JF - Expert Opinion on Drug Discovery

SN - 1746-0441

IS - 4

ER -