Normal Midbrain Organoid Model

Parkinson’s disease (PD) is a common neurodegenerative disease resulting from the selective degeneration of dopaminergic neurons caused by the accumulation of Lewy bodies. It mainly affects the normal functions of the motor system. Current cell and animal models fail to recapitulate human PD etiology, leading to no radical treatment. Creative Biolabs has successfully established 3D biology platform and can provide normal midbrain organoid model for PD mechanism research.

Construction of Normal Midbrain Organoid Models

We employ the common approach to generate normal midbrain organoids from embryoid bodies. This protocol involves the use of hydrogels and orbital shakers embedding by sequential patterning or by simultaneous patterning methods. In the sequential patterning, we conduct the midbrain specification operation by using dual SMAD inhibitors and WNT modulation. Then the midbrain floor plate is induced by Sonic Hedgehog (SHH) modulation and FGF8. And finally, the differentiation and maturation step is carried out by using multiple neurotrophic factors. By contrast, the midbrain specification and floor plate induction are performed simultaneously in the simultaneous patterning protocol. Other steps are similar to the sequential method other than involving additional supplements.

Advantages of Normal Midbrain Organoid Models

Organoids are self-organized 3D aggregates derived from stem cells. At present, they are the most complex and most advanced culture technology reproducing physiological tissues in vitro. They provide new insights into human biology and disease, and have distinct advantages over 2D cell culture and animal models in PD research.

Such models allow to reproduce complex interactions between midbrain-specific dopaminergic neurons (mDANs) and other cells in the central nervous system (CNS) in vitro.
They display inherent features of the prenatal midbrain in terms of gene expression profiles, which is challenging for conventional 2D derivation methods.
Culturing these midbrain organoids help the biology modeling, which is superior to the 2D stem cell culture technology in cellular structure and heterogeneity aspects.
Besides, they can be easily expanded to obtain enormous disease-relevant mDANs stably and rapidly, which is very helpful for drug discovery in PD research.
They display dopaminergic neuron markers as well as midbrain floor plate markers and retain the differentiation capability of dopaminergic neurons, which show great potential for modeling PD.

Fig 1. hMO differentiation for in vivo human midbrain development. Fig 1. Summarized hMO differentiation strategies.¹

Applications of Normal Midbrain Organoid Models

In the PD research process, Renner et al constructed the automated midbrain organoids (AMOs) and found they are universally applicable to a variety of analyses and assay procedures. As shown in Fig.1, the schematic overview clearly displays the compatibility of the AMOs with high throughput technologies. Of course, the applications of normal midbrain organoids are not restricted to the PD area, they also create many possibilities for other brain diseases.

Related Services

As a reputable biology company, Creative Biolabs has successfully entered this 3D biology field. Through continuous innovation, we have launched a series of popular organoids, which are highly customized to respond to various research needs. In addition, we also provide 3D biology-based assay services and are confident to win your satisfaction. Please feel free to contact us at your convenience to discuss your project.

References

Galet, B.; et al. Patient-derived midbrain organoids to explore the molecular basis of Parkinson's disease. 2020, 11: 1005. Distributed under Open Access License CC BY 4.0, without modification.
Smits L.; et al. Midbrain organoids: a new tool to investigate Parkinson's disease. Front Cell Dev Biol. 2020, 8: 359. Distributed under Open Access License CC BY 4.0.
Shankaran, A.; et al. Advances in development and application of human organoids. 3 Biotech. 2021, 11(6): 257. Distributed under Open Access License CC BY 4.0.