Brain Organoids-A Bottom-Up Approach for Studying Human Neurodevelopment

Overview

Journal Bioengineering (Basel)

Date 2019 Jan 24

PMID 30669275

Citations 19

Authors

Eyal Karzbrun

Orly Reiner

Affiliations

Soon will be listed here.

Abstract

Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific disorders. However, there are still major differences between the in vitro systems and in vivo development. This is in part due to the challenge of engineering a suitable culture platform that will support proper development. In this review, we discuss the similarities and differences of human brain organoid systems in comparison to embryonic development. We then describe how organoids are used to model neurodevelopmental diseases. Finally, we describe challenges in organoid systems and how to approach these challenges using complementary bioengineering techniques.

Citing Articles

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References

Chambers S, Fasano C, Papapetrou E, Tomishima M, Sadelain M, Studer L . Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009; 27(3):275-80. PMC: 2756723. DOI: 10.1038/nbt.1529. View

Karzbrun E, Kshirsagar A, Cohen S, Hanna J, Reiner O . Human Brain Organoids on a Chip Reveal the Physics of Folding. Nat Phys. 2018; 14(5):515-522. PMC: 5947782. DOI: 10.1038/s41567-018-0046-7. View

Rakic P . Evolution of the neocortex: a perspective from developmental biology. Nat Rev Neurosci. 2009; 10(10):724-35. PMC: 2913577. DOI: 10.1038/nrn2719. View

Camp J, Badsha F, Florio M, Kanton S, Gerber T, Wilsch-Brauninger M . Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci U S A. 2015; 112(51):15672-7. PMC: 4697386. DOI: 10.1073/pnas.1520760112. View

Otani T, Marchetto M, Gage F, Simons B, Livesey F . 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size. Cell Stem Cell. 2016; 18(4):467-80. PMC: 4826446. DOI: 10.1016/j.stem.2016.03.003. View

Workman A, Charvet C, Clancy B, Darlington R, Finlay B . Modeling transformations of neurodevelopmental sequences across mammalian species. J Neurosci. 2013; 33(17):7368-83. PMC: 3928428. DOI: 10.1523/JNEUROSCI.5746-12.2013. View

Kim J, Fluri D, Marchan R, Boonen K, Mohanty S, Singh P . 3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis. J Biotechnol. 2015; 205:24-35. DOI: 10.1016/j.jbiotec.2015.01.003. View

Long K, Newland B, Florio M, Kalebic N, Langen B, Kolterer A . Extracellular Matrix Components HAPLN1, Lumican, and Collagen I Cause Hyaluronic Acid-Dependent Folding of the Developing Human Neocortex. Neuron. 2018; 99(4):702-719.e6. DOI: 10.1016/j.neuron.2018.07.013. View

Vollert I, Seiffert M, Bachmair J, Sander M, Eder A, Conradi L . In vitro perfusion of engineered heart tissue through endothelialized channels. Tissue Eng Part A. 2013; 20(3-4):854-63. DOI: 10.1089/ten.TEA.2013.0214. View

10.

Pasca A, Sloan S, Clarke L, Tian Y, Makinson C, Huber N . Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods. 2015; 12(7):671-8. PMC: 4489980. DOI: 10.1038/nmeth.3415. View

11.

Kolesky D, Homan K, Skylar-Scott M, Lewis J . Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci U S A. 2016; 113(12):3179-84. PMC: 4812707. DOI: 10.1073/pnas.1521342113. View

12.

Lee G, Lee J, Lee G, Joung W, Kim S, Lee S . Networked concave microwell arrays for constructing 3D cell spheroids. Biofabrication. 2017; 10(1):015001. DOI: 10.1088/1758-5090/aa9876. View

13.

Kelava I, Lancaster M . Dishing out mini-brains: Current progress and future prospects in brain organoid research. Dev Biol. 2016; 420(2):199-209. PMC: 5161139. DOI: 10.1016/j.ydbio.2016.06.037. View

14.

Kang H, Kawasawa Y, Cheng F, Zhu Y, Xu X, Li M . Spatio-temporal transcriptome of the human brain. Nature. 2011; 478(7370):483-9. PMC: 3566780. DOI: 10.1038/nature10523. View

15.

Picollet-Dhahan N, Dolega M, Liguori L, Marquette C, Le Gac S, Gidrol X . A 3D Toolbox to Enhance Physiological Relevance of Human Tissue Models. Trends Biotechnol. 2016; 34(9):757-769. DOI: 10.1016/j.tibtech.2016.06.012. View

16.

Zhu W, Qu X, Zhu J, Ma X, Patel S, Liu J . Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. Biomaterials. 2017; 124:106-115. PMC: 5330288. DOI: 10.1016/j.biomaterials.2017.01.042. View

17.

Li Y, Muffat J, Omer A, Bosch I, Lancaster M, Sur M . Induction of Expansion and Folding in Human Cerebral Organoids. Cell Stem Cell. 2017; 20(3):385-396.e3. PMC: 6461394. DOI: 10.1016/j.stem.2016.11.017. View

18.

Nakano T, Ando S, Takata N, Kawada M, Muguruma K, Sekiguchi K . Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell. 2012; 10(6):771-785. DOI: 10.1016/j.stem.2012.05.009. View

19.

Li R, Sun L, Fang A, Li P, Wu Q, Wang X . Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease. Protein Cell. 2017; 8(11):823-833. PMC: 5676597. DOI: 10.1007/s13238-017-0479-2. View

20.

Khazipov R, Sirota A, Leinekugel X, Holmes G, Ben-Ari Y, Buzsaki G . Early motor activity drives spindle bursts in the developing somatosensory cortex. Nature. 2004; 432(7018):758-61. DOI: 10.1038/nature03132. View