ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Organoids and Organ-On-A-Chip
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1684315
This article is part of the Research TopicAdvancing Disease Modeling and Therapy with Organoids and Organ-on-a-ChipView all articles
Upscaling: Efficient generation of human lung organoids from induced pluripotent stem cells using a stirring bioreactor
Provisionally accepted
- University of Duisburg-Essen, Duisburg, Germany
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Human induced pluripotent stem cells (iPSCs) can be successfully differentiated into complex (three-dimensional) lung spheroids or organoids and have thus proven to be promising in vitro tools that provide a robust system for simulating lung disease and modeling drug response. We previously described a very simple and practical protocol for producing iPSC-derived lung organoids (iPSC-LuOrgs) in ultra-low attachment plates without relying on a gel-like extracellular matrix. Here, we attempted to produce these organoids in a stirred-tank bioreactor equipped with a unique membrane stirrer and compared this type of up-scaled and more automated cultivation with the manual variant. For this purpose, detailed morphological and molecular analyses, including single-cell RNA sequencing, of the differently generated LuOrgs were performed. Just like in the manual variant, using the bioreactor morphologically comparable lung organoids could be obtained that showed a very similar cellular composition. This generation can also be considered as animal component-free production. These freely floating LuOrgs are now available in large numbers for the investigation of, for example, cancer therapy approaches as a new and patient-oriented in vitro platform.
Keywords: Lung, Organoids, upscaling, 3D culture, bioreactor, Bioengineering, IPSC
Received: 12 Aug 2025; Accepted: 08 Oct 2025.
Copyright: © 2025 Klein, Budeus, Kroepel, Sevindik and Buttler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Diana Klein, diana.klein@uk-essen.de
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