The Brain Organoids

  • Challenges in research on the human brain

  • Opportunities on organoid technology in scientific research

  • Application of brain organoids in research

  • Scientists make brain organoids with eye structure

  • Using brain organoids as models in research on ageing and brain tumour

  • Future development of brain organoid technology

  • Our selected composition for brain organoid

Challenges in research on human brain

  • Our current understanding of the human brain is mostly dependent on brain specimens from dead bodies, mainly due to ethical issues [1].
  • Animal models have been used in scientific research however there are several discrepancies compared to the human brain [1].
  • It is very challenging for scientists to study the development of the human central nervous system (CNS) and related diseases by using animal models due to these discrepancies [1].
  • The complexity of the human brain made it difficult for scientists to study many brain disorders in model organisms called for the establishment of an in vitro model of human brain development [2]. 

Opportunities on organoid technology in scientific research

  • The emergence of 3-D organoids had brought a lot of attention to regenerative medicine [1].
  • Organoid models include three-dimensional (3D) cell culture systems that closely resemble in vivo organs or tissue.
  • These 3D systems reproduce the complex spatial morphology of differentiated tissue to allow biologically relevant cell-to-cell and cell-to-matrix interactions, which ideally will share similar physiological responses with in-vivo differentiated tissues. 

Application of brain organoids in research

  • Some studies from the past have shown that brain organoids can recapitulate some key features of the human brain, including cellular distribution and organization, physiological structure, electrical activities, and neuronal networks [1].
  • Brain organoids have become a model with a wide range of applications in the research field, not limited to neurodevelopmental disorders like autism spectrum disorders (ASD) and Down Syndrome, but also neurodegenerative disorders like Alzheimer’s disease and Parkinson’s Disease, infectious diseases, brain tumour, toxicology, and mental illness [1].

Scientists make brain organoids with eye structure

  • Recent news published by the American Association for the Advancement of Science (AAAS) reported a journal article on brain organoids from Cell Stem Cell. Gabriel et al. found that human induced pluripotent stem cells (iPSCs) can be used to generate brain organoids containing an eye structure, the optic cup, that are sensitive to light [3].
  • In the past, the building of optic cups from pluripotent stem cells aimed at generating the pure retina [3].
  • It is the first time for scientists to integrate optic cups into brain organoids. 

Using brain organoids as model in research on aging and brain tumour

  • Besides, there are some more exciting findings on brain organoids published by Nature Scientific Report and Nature Aging and Mechanisms of Disease recently.
  • By using brain organoid as a model, Jermakowicz et al identified a novel protein inhibitor, UM-002, that can reduce the cell proliferation and invasion of a brain tumour in vitro [4] while Shaker et al. found that Klotho, a type 1 transmembrane protein, inhibits neuronal senescence in human brain organoids [5]. 

Future development of brain organoid technology

  • Brain organoids provide an excellent model for scientists to understand the development, ageing and evolvement of the human brain yet there are still a lot of technical challenges in terms of brain organoid harvest, organoid generation, and culture, as well as the standardization of organoids in the research setting [1].
  • In the future, one of the developments of brain organoid technology will be to resolve these issues and look for technical advancement for better research outcomes [1].

Selected compositions for brain organoid culture by Lab-A-Porter

EGF

EGF is a potent growth factor that stimulates the proliferation of various epidermal and epithelial cells. It has been shown to inhibit gastric secretion and be involved in wound healing.                                                                              

Noggin

Noggin belongs to a group of diffusible proteins that bind to ligands of the TGF-β family and regulate their activity by inhibiting their access to signalling receptors.                                                                                                                                          

FGF basic

FGF-basic is one of 23 known members of the FGF family. Proteins of this family play a central role during prenatal development, postnatal growth and regeneration of a variety of tissues, by promoting cellular proliferation and differentiation.

DKK-1

DKK-1 is a member of the DKK protein family which also includes DKK-2, DKK-3 and DKK-4.                                                                                                                                                                                                                                                                        

BDNF

BDNF is a member of the NGF family of neurotrophic growth factors. Like other members of this family, BDNF supports neuron proliferation and survival.                                                                                                                                                                      

GDNF

GDNF is a disulfide-linked, homodimeric neurotrophic factor structurally related to Artemin, Neurturin and Persephin.  These proteins belong to the cysteine-knot superfamily of growth factors that assume stable dimeric protein structures. 

MK-2006

MK-2206 is a highly allosteric selective Akt1,2,3 (IC50 5nM, 12nM, 65nM) inhibitor. It is reported to inhibit the proliferation of cancer cell lines when used synergistically with cytotoxic agents such as erlotinib or lapatinib and significantly enhances cell apoptosis.

GDC-0068

GDC-0068 is a potent and selective pan-AKT inhibitor that targets Akt1, Akt2, and Akt3 over other kinases. It inhibits cell cycle progression and exhibits antitumor properties, reducing the viability of cancer cell lines.                                                                                          

Dorsomorphin

Dorsomorphin is a potent and selective inhibitor of the BMP pathway through the ALK2, ALK3, and ALK6 receptors. It is also a selective and reversible inhibitor of the AMP-activated protein kinase (AMPK). Dorsomorphin is reported to be useful in promoting specific cell differentiation and inducing cancer cell line autophagy.                                                                                                                                     

Y-27632

Y-27632 is a selective inhibitor of Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) family of protein kinases that selectively competes with ATP for binding to the catalytic site. It is reported to diminish dissociation-induced apoptosis, increase cloning efficiency, and facilitate subcloning after gene transfer in human embryonic stem cells (hES).

PeproTech and Biogems products are for research use only (RUO) and are NOT FOR THERAPEUTIC OR DIAGNOSTIC USE. 

References:

1. Shou, Yikai et al. “The Application of Brain Organoids: From Neuronal Development to Neurological Diseases.” Frontiers in cell and developmental biology vol. 8 579659. 22 Oct. 2020, doi:10.3389/fcell.2020.579659

2. Organoid. ‘’https://www.peprotech.com/download/2027/organoids-brochure-2’’. Peprotech Inc., 2021. 

3. Brain organoids develop optic cups that respond to light. ‘’ https://www.eurekalert.org/news-releases/925127’’. American Association for the Advancement of Science, 17th August 2021. 

4. Jermakowicz, Anna M et al. “The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion.” Scientific Reports vol. 11,1 23370. 3 Dec. 2021, doi:10.1038/s41598-021-02584-6

5. Shaker, Mohammed R et al. “Klotho inhibits neuronal senescence in human brain organoids.” NPJ aging and mechanisms of disease vol. 7,1 18. 2 Aug. 2021, doi:10.1038/s41514-021-00070-x

PeproTech and Biogems products are for research use only (RUO) and are NOT FOR THERAPEUTIC OR DIAGNOSTIC USE. 

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