Issue 20, 2018

Millifluidic culture improves human midbrain organoid vitality and differentiation


Human midbrain-specific organoids (hMOs) serve as an experimental in vitro model for studying the pathogenesis of Parkinson's disease (PD). In hMOs, neuroepithelial stem cells (NESCs) give rise to functional midbrain dopaminergic (mDA) neurons that are selectively degenerating during PD. A limitation of the hMO model is an under-supply of oxygen and nutrients to the densely packed core region, which leads eventually to a “dead core”. To reduce this phenomenon, we applied a millifluidic culture system that ensures media supply by continuous laminar flow. We developed a computational model of oxygen transport and consumption in order to predict oxygen levels within the hMOs. The modelling predicts higher oxygen levels in the hMO core region under millifluidic conditions. In agreement with the computational model, a significantly smaller “dead core” was observed in hMOs cultured in a bioreactor system compared to those ones kept under conventional shaking conditions. Comparing the necrotic core regions in the organoids with those obtained from the model allowed an estimation of the critical oxygen concentration necessary for ensuring cell vitality. Besides the reduced “dead core” size, the differentiation efficiency from NESCs to mDA neurons was elevated in hMOs exposed to medium flow. Increased differentiation involved a metabolic maturation process that was further developed in the millifluidic culture. Overall, bioreactor conditions that improve hMO quality are worth considering in the context of advanced PD modelling.

Graphical abstract: Millifluidic culture improves human midbrain organoid vitality and differentiation

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Article information

Article type
25 Feb 2018
10 May 2018
First published
11 Sep 2018
This article is Open Access
Creative Commons BY license

Lab Chip, 2018,18, 3172-3183

Millifluidic culture improves human midbrain organoid vitality and differentiation

E. Berger, C. Magliaro, N. Paczia, A. S. Monzel, P. Antony, C. L. Linster, S. Bolognin, A. Ahluwalia and J. C. Schwamborn, Lab Chip, 2018, 18, 3172 DOI: 10.1039/C8LC00206A

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