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 language | English (US) |
|---|---|
| Pages (from-to) | 379-386 |
| Number of pages | 8 |
| Journal | Expert Opinion on Drug Discovery |
| Volume | 14 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 3 2019 |
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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 journal › Review article
}
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
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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
C2 - 30831040
AN - SCOPUS:85062993018
VL - 14
SP - 379
EP - 386
JO - Expert Opinion on Drug Discovery
JF - Expert Opinion on Drug Discovery
SN - 1746-0441
IS - 4
ER -