Advances in 3D neural, vascular and neurovascular models for drug testing and regenerative medicine

被引：13

作者：

Fernandes, Diogo C. ^{[1
,2
]}

Reis, Rui L. ^{[1
,2
]}

Oliveira, J. Miguel ^{[1
,2
]}

机构：

[1] Univ Minho, Headquarters European Inst Excellence Tissue Engn, 3Bs Res Grp, I3Bs Res Inst Biomat Biodegradables & Biomimet, AvePk, P-4805017 Barco Gmr, Portugal

[2] ICVS 3Bs Portuguese Govt Associate Lab, P-4805017 Braga, Portugal

来源：

DRUG DISCOVERY TODAY | 2021年 / 26卷 / 03期

关键词：

BLOOD-BRAIN-BARRIER; CEREBRAL ORGANOIDS; ELECTRICAL-RESISTANCE; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; IMMUNE-SYSTEM; PERMEABILITY; DISEASE; NEURONS; VIRUS;

D O I：

10.1016/j.drudis.2020.11.009

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Clinical trials continue to fall short regarding drugs to effectively treat brain-affecting diseases. Although there are many causes of these shortcomings, the most relevant are the inability of most therapeutic agents to cross the blood?brain barrier (BBB) and the failure to translate effects from animal models to patients. In this review, we analyze the most recent developments in BBB, neural, and neurovascular models, analyzing their impact on the drug development process by considering their quantitative and phenotypical characterization. We offer a perspective of the state-of-the-art of the models that could revolutionize the pharmaceutical industry. Clinical trials continue to fall short regarding drugs to effectively treat brain-affecting diseases. Although there are many causes of these shortcomings, the most relevant are the inability of most therapeutic agents to cross the blood?brain barrier (BBB) and the failure to translate effects from animal models to patients. In this review, we analyze the most recent developments in BBB, neural, and neurovascular models, analyzing their impact on the drug development process by considering their quantitative and phenotypical characterization. We offer a perspective of the state-of-the-art of the models that could revolutionize the pharmaceutical industry.

引用

页码：754 / 768

页数：15

共 122 条

[61] An in vivo model of functional and vascularized human brain organoids [J].

Mansour, Abed AlFatah ;

Goncalves, J. Tiago ;

Bloyd, Cooper W. ;

Li, Hao ;

Fernandes, Sarah ;

Quang, Daphne ;

Johnston, Stephen ;

Parylak, Sarah L. ;

Jin, Xin ;

Gage, Fred H. .

NATURE BIOTECHNOLOGY, 2018, 36 (05) :432-+

[62] A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells [J].

Maoz, Ben M. ;

Herland, Anna ;

FitzGerald, Edward A. ;

Grevesse, Thomas ;

Vidoudez, Charles ;

Pacheco, Alan R. ;

Sheehy, Sean P. ;

Park, Tae-Eun ;

Dauth, Stephanie ;

Mannix, Robert ;

Budnik, Nikita ;

Shores, Kevin ;

Cho, Alexander ;

Nawroth, Janna C. ;

Segre, Daniel ;

Budnik, Bogdan ;

Ingber, Donald E. ;

Parker, Kevin Kit .

NATURE BIOTECHNOLOGY, 2018, 36 (09) :865-+

[63] A 3D Real-Scale, Biomimetic, and Biohybrid Model of the Blood-Brain Barrier Fabricated through Two-Photon Lithography [J].

Marino, Attilio ;

Tricinci, Omar ;

Battaglini, Matteo ;

Filippeschi, Carlo ;

Mattoli, Virgilio ;

Sinibaldi, Edoardo ;

Ciofani, Gianni .

SMALL, 2018, 14 (06)

[64] Biology- Inspired Microphysiological Systems to Advance Patient Benefit and Animal Welfare in Drug Development [J].

Marx, Uwe ;

Akabane, Takafumi ;

Andersson, Tommy B. ;

Baker, Elizabeth ;

Beilmann, Mario ;

Beken, Sonja ;

Brendler-Schwaab, Susanne ;

Cirit, Murat ;

David, Rhiannon ;

Dehne, Eva-Maria ;

Durieux, Isabell ;

Ewart, Lorna ;

Fitzpatrick, Suzanne C. ;

Frey, Olivier ;

Fuchs, Florian ;

Griffith, Linda G. ;

Hamilton, Geraldine A. ;

Hartung, Thomas ;

Hoeng, Julia ;

Hogberg, Helena ;

Hughes, David J. ;

Ingber, Donald E. ;

Iskandar, Anita ;

Kanamori, Toshiyuki ;

Kojima, Hajime ;

Kuehnl, Jochen ;

Leist, Marcel ;

Li, Bo ;

Loskill, Peter ;

Mendrick, Donna L. ;

Neumann, Thomas ;

Pallocca, Giorgia ;

Rusyn, Ivan ;

Smirnova, Lena ;

Steger-Hartmann, Thomas ;

Tagle, Danilo A. ;

Tonevitsky, Alexander ;

Tsyb, Sergej ;

Trapecar, Martin ;

van de Water, Bob ;

van den Eynden-van Raaij, Janny ;

Vultoy, Paul ;

Watanabe, Kengo ;

Wolf, Armin ;

Zhou, Xiaobing ;

Roth, Adrian .

ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION, 2020, 37 (03) :365-394

[65] PERMEABILITY OF BLOOD-BRAIN-BARRIER TO VARIOUS SIZED MOLECULES [J].

MAYHAN, WG ;

HEISTAD, DD .

AMERICAN JOURNAL OF PHYSIOLOGY, 1985, 248 (05) :H712-H718

[66] Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan [J].

Miyata, Shinji ;

Kitagawa, Hiroshi .

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2017, 1861 (10) :2420-2434

[67] Morphological assessment of radical prostatectomy specimens. A protocol with clinical relevance [J].

Montironi, R ;

Mazzucchelli, R ;

Kwast, T .

VIRCHOWS ARCHIV, 2003, 442 (03) :211-217

[68] Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells [J].

Monzel, Anna S. ;

Smits, Lisa M. ;

Hemmer, Kathrin ;

Hachi, Siham ;

Moreno, Edinson Lucumi ;

van Wuellen, Thea ;

Jarazo, Javier ;

Walter, Jonas ;

Bruggemann, Inga ;

Boussaad, Ibrahim ;

Berger, Emanuel ;

Fleming, Ronan M. T. ;

Bolognin, Silvia ;

Schwamborn, Jens C. .

STEM CELL REPORTS, 2017, 8 (05) :1144-1154

[69] An isogenic hiPSC-derived BBB-on-a-chip [J].

Motallebnejad, Pedram ;

Thomas, Andrew ;

Swisher, Sarah L. ;

Azarin, Samira M. .

BIOMICROFLUIDICS, 2019, 13 (06)

[70] A Reconfigurable In Vitro Model for Studying the Blood-Brain Barrier [J].

Moya, Monica L. ;

Triplett, Michael ;

Simon, Melinda ;

Alvarado, Javier ;

Booth, Ross ;

Osburn, Joanne ;

Soscia, David ;

Qian, Fang ;

Fischer, Nicholas O. ;

Kulp, Kristen ;

Wheeler, Elizabeth K. .

ANNALS OF BIOMEDICAL ENGINEERING, 2020, 48 (02) :780-793

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