In Vitro Models of CNS Barriers

N Joan Abbott; Siti R. Yusof; Andreas Reichel; Diana E M Dolman; Jane E Preston

doi:10.1007/978-3-030-88773-5_8

In Vitro Models of CNS Barriers

N Joan Abbott, Siti R. Yusof, Andreas Reichel, Diana E M Dolman, Jane E Preston^*

^*Corresponding author for this work

Institute of Pharmaceutical Science

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

1 Citation (Scopus)

Abstract

In vitro models of the blood-brain barrier provide valuable mechanistic information and useful assay systems for drug discovery and delivery. However, it is important to take into account issues including species differences and to what extent features of the in vivo BBB are retained in cell culture. The history and applications of a primary cells, immortalized cell lines, and stem cell-derived BBB models are reviewed, with evaluation of their strengths and weaknesses, in selecting and optimizing a suitable model for particular applications. Understanding of the unstirred water layers gives insights into the “intrinsic permeability” of the membrane, and proteomic and transcriptomic studies have expanded the characterization of the barrier function. Technologies to derive brain endothelium from human stem cells create 3D models of the neurovascular unit, and miniaturize “organ-on-a-chip” flow systems give great promise for the future. All these technologies are crucial to translate BBB research to viable treatment options for patients.

Original language	English
Title of host publication	AAPS Advances in the Pharmaceutical Sciences Series
Subtitle of host publication	Physiological Concepts, Methodologies and Approaches
Editors	de Lange Elizabeth, Margareta Hammarlund-Udenaes, Robert Thorne
Place of Publication	USA
Publisher	Springer, Cham
Chapter	8
Pages	211–254
Number of pages	44
Volume	33
Edition	2
ISBN (Electronic)	978-3-030-88773-5
ISBN (Print)	978-3-030-88772-8
DOIs	https://doi.org/10.1007/978-3-030-88773-5_8
Publication status	Published - 25 May 2022

Publication series

Name	AAPS Advances in the Pharmaceutical Sciences Series
Volume	33
ISSN (Print)	2210-7371
ISSN (Electronic)	2210-738X

Keywords

Blood-brain barrier
In vitro models
Endothelia
Astrocyte
Pericyte
TEER
Primary cells
bEND.3
hCMEC/D3
iPSC
IVIVC

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Cite this

Abbott, N. J., Yusof, S. R., Reichel, A., Dolman, D. E. M., & Preston, J. E. (2022). In Vitro Models of CNS Barriers. In D. L. Elizabeth, M. Hammarlund-Udenaes, & R. Thorne (Eds.), AAPS Advances in the Pharmaceutical Sciences Series: Physiological Concepts, Methodologies and Approaches (2 ed., Vol. 33, pp. 211–254). (AAPS Advances in the Pharmaceutical Sciences Series; Vol. 33). Springer, Cham. https://doi.org/10.1007/978-3-030-88773-5_8

Abbott, N Joan ; Yusof, Siti R. ; Reichel, Andreas et al. / In Vitro Models of CNS Barriers. AAPS Advances in the Pharmaceutical Sciences Series: Physiological Concepts, Methodologies and Approaches. editor / de Lange Elizabeth ; Margareta Hammarlund-Udenaes ; Robert Thorne. Vol. 33 2. ed. USA : Springer, Cham, 2022. pp. 211–254 (AAPS Advances in the Pharmaceutical Sciences Series).

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title = "In Vitro Models of CNS Barriers",

abstract = "In vitro models of the blood-brain barrier provide valuable mechanistic information and useful assay systems for drug discovery and delivery. However, it is important to take into account issues including species differences and to what extent features of the in vivo BBB are retained in cell culture. The history and applications of a primary cells, immortalized cell lines, and stem cell-derived BBB models are reviewed, with evaluation of their strengths and weaknesses, in selecting and optimizing a suitable model for particular applications. Understanding of the unstirred water layers gives insights into the “intrinsic permeability” of the membrane, and proteomic and transcriptomic studies have expanded the characterization of the barrier function. Technologies to derive brain endothelium from human stem cells create 3D models of the neurovascular unit, and miniaturize “organ-on-a-chip” flow systems give great promise for the future. All these technologies are crucial to translate BBB research to viable treatment options for patients.",

keywords = "Blood-brain barrier, In vitro models, Endothelia, Astrocyte, Pericyte, TEER, Primary cells, bEND.3, hCMEC/D3, iPSC, IVIVC",

author = "Abbott, {N Joan} and Yusof, {Siti R.} and Andreas Reichel and Dolman, {Diana E M} and Preston, {Jane E}",

note = "Funding Information: We are grateful for discussions and comments from many colleagues especially Prof. Maria Deli, Dr. Alex Avdeef, and Prof. Margareta Hammarlund-Udenaes and for redrawing of Fig. 8.1 by Dr. Robert Thorne and for Fig. 8.4 from Dr. Anika Hartz and Dr. Bjoern Bauer. Publisher Copyright: {\textcopyright} 2022, American Association of Pharmaceutical Scientists.",

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Abbott, NJ, Yusof, SR, Reichel, A, Dolman, DEM & Preston, JE 2022, In Vitro Models of CNS Barriers. in DL Elizabeth, M Hammarlund-Udenaes & R Thorne (eds), AAPS Advances in the Pharmaceutical Sciences Series: Physiological Concepts, Methodologies and Approaches. 2 edn, vol. 33, AAPS Advances in the Pharmaceutical Sciences Series, vol. 33, Springer, Cham, USA, pp. 211–254. https://doi.org/10.1007/978-3-030-88773-5_8

In Vitro Models of CNS Barriers. / Abbott, N Joan; Yusof, Siti R.; Reichel, Andreas et al.
AAPS Advances in the Pharmaceutical Sciences Series: Physiological Concepts, Methodologies and Approaches. ed. / de Lange Elizabeth; Margareta Hammarlund-Udenaes; Robert Thorne. Vol. 33 2. ed. USA: Springer, Cham, 2022. p. 211–254 (AAPS Advances in the Pharmaceutical Sciences Series; Vol. 33).

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

TY - CHAP

T1 - In Vitro Models of CNS Barriers

AU - Abbott, N Joan

AU - Yusof, Siti R.

AU - Reichel, Andreas

AU - Dolman, Diana E M

AU - Preston, Jane E

N1 - Funding Information: We are grateful for discussions and comments from many colleagues especially Prof. Maria Deli, Dr. Alex Avdeef, and Prof. Margareta Hammarlund-Udenaes and for redrawing of Fig. 8.1 by Dr. Robert Thorne and for Fig. 8.4 from Dr. Anika Hartz and Dr. Bjoern Bauer. Publisher Copyright: © 2022, American Association of Pharmaceutical Scientists.

PY - 2022/5/25

Y1 - 2022/5/25

N2 - In vitro models of the blood-brain barrier provide valuable mechanistic information and useful assay systems for drug discovery and delivery. However, it is important to take into account issues including species differences and to what extent features of the in vivo BBB are retained in cell culture. The history and applications of a primary cells, immortalized cell lines, and stem cell-derived BBB models are reviewed, with evaluation of their strengths and weaknesses, in selecting and optimizing a suitable model for particular applications. Understanding of the unstirred water layers gives insights into the “intrinsic permeability” of the membrane, and proteomic and transcriptomic studies have expanded the characterization of the barrier function. Technologies to derive brain endothelium from human stem cells create 3D models of the neurovascular unit, and miniaturize “organ-on-a-chip” flow systems give great promise for the future. All these technologies are crucial to translate BBB research to viable treatment options for patients.

AB - In vitro models of the blood-brain barrier provide valuable mechanistic information and useful assay systems for drug discovery and delivery. However, it is important to take into account issues including species differences and to what extent features of the in vivo BBB are retained in cell culture. The history and applications of a primary cells, immortalized cell lines, and stem cell-derived BBB models are reviewed, with evaluation of their strengths and weaknesses, in selecting and optimizing a suitable model for particular applications. Understanding of the unstirred water layers gives insights into the “intrinsic permeability” of the membrane, and proteomic and transcriptomic studies have expanded the characterization of the barrier function. Technologies to derive brain endothelium from human stem cells create 3D models of the neurovascular unit, and miniaturize “organ-on-a-chip” flow systems give great promise for the future. All these technologies are crucial to translate BBB research to viable treatment options for patients.

KW - Blood-brain barrier

KW - In vitro models

KW - Endothelia

KW - Astrocyte

KW - Pericyte

KW - TEER

KW - Primary cells

KW - bEND.3

KW - hCMEC/D3

KW - iPSC

KW - IVIVC

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U2 - 10.1007/978-3-030-88773-5_8

DO - 10.1007/978-3-030-88773-5_8

M3 - Chapter

SN - 978-3-030-88772-8

VL - 33

T3 - AAPS Advances in the Pharmaceutical Sciences Series

SP - 211

EP - 254

BT - AAPS Advances in the Pharmaceutical Sciences Series

A2 - Elizabeth, de Lange

A2 - Hammarlund-Udenaes, Margareta

A2 - Thorne, Robert

PB - Springer, Cham

CY - USA

ER -

Abbott NJ, Yusof SR, Reichel A, Dolman DEM, Preston JE. In Vitro Models of CNS Barriers. In Elizabeth DL, Hammarlund-Udenaes M, Thorne R, editors, AAPS Advances in the Pharmaceutical Sciences Series: Physiological Concepts, Methodologies and Approaches. 2 ed. Vol. 33. USA: Springer, Cham. 2022. p. 211–254. (AAPS Advances in the Pharmaceutical Sciences Series). doi: 10.1007/978-3-030-88773-5_8

In Vitro Models of CNS Barriers

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