Midbrain organoids

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Junghyun Jo, Huck Hui Ng (A*STAR Genome Institute of Singapore), Hyunsoo Shawn Je (Duke-NUS Medical School) and 20 co-authors (23 in all), including Thomas Hyde, Joel Kleinman and Daniel Weinberger of the Lieber Institute for Brain Development (Baltimore) and Eng King Tan. Funding came from Singapore's Ministry of Education, A*STAR, Duke-NUS and the National Medical Research Council.

What happened

The team coaxed human stem cells into 3D organoids (pea-sized cell clusters, here about 2–3 mm) with layered structure and midbrain markers. They contained electrically active dopamine neurons that released dopamine. Unlike dopamine neurons from flat dish cultures or mouse-cell organoids, these also produced neuromelanin-like granules similar to those in human substantia nigra tissue (the dark pigment that marks the neurons lost in Parkinson's). Cell Stem Cell 19:248–257, published 4 August 2016. The paper reported no disease modelling or drug tests.

Why it moved us toward a cure

It offered a dish system closer to human midbrain tissue than flat cultures, one that can be grown from patient cells (landmark 47) and scaled for drug screening. In 2019, Smits and colleagues (University of Luxembourg) grew midbrain organoids from patients with the LRRK2 G2019S mutation. They had fewer, simpler dopamine neurons than controls and raised FOXA2 (a floor-plate gene needed to make these neurons), suggesting a developmental defect (npj Parkinson's Disease 5, article 5). The dopamine neuron recipe itself comes from landmark 17.

Outcome

Open. The 2016 paper is a method, not a finding about disease, and the 2019 organoid result is from a single mutation. The sources here do not show a treatment developed through organoid work. A Cell Stem Cell commentary accompanied the paper; no correction or retraction was found (Crossref, Europe PMC).

Sources

• Jo et al., Cell Stem Cell 2016;19(2):248–257, DOI 10.1016/j.stem.2016.07.005, PMID 27476966 (abstract, authors and funding read via Europe PMC, PMC5510242) · Asian Scientist report
• Smits et al., npj Parkinson's Dis 2019;5:5, DOI 10.1038/s41531-019-0078-4 (abstract via Europe PMC, PMID 30963107)
• Not yet verified: organoid batch variability and immaturity; use of organoids in drug discovery programmes.