4.4 Article

Scalable expansion of iPSC and their derivatives across multiple lineages

Journal

REPRODUCTIVE TOXICOLOGY
Volume 112, Issue -, Pages 23-35

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2022.05.007

Keywords

Induced pluripotent stem cells; Cell banking; EBiSC; Differentiation; Upscaling; Bioprocessing; Cell processing; Suspension-based bioreactor

Funding

  1. Innovative Medicines Initiative 2 Joint Undertaking (JU) [821362]
  2. European Union's Horizon 2020 research and innovation programme
  3. EFPIA

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Induced pluripotent stem cells (iPSCs), with their ability to differentiate into various cell types, have become an important tool in biomedical research. This article discusses the development of scalable methods for large-scale production of iPSCs using 3D suspension culture platforms. It also highlights the establishment of robust differentiation protocols for cardiac, neural, and hepatic cell types to meet the increasing demand for research tools.
Induced pluripotent stem cell (iPSC) technology enabled the production of pluripotent stem cell lines from somatic cells from a range of known genetic backgrounds. Their ability to differentiate and generate a wide variety of cell types has resulted in their use for various biomedical applications, including toxicity testing. Many of these iPSC lines are now registered in databases and stored in biobanks such as the European Bank for induced pluripotent Stem Cells (EBiSC), which can streamline the quality control and distribution of these individual lines. To generate the quantities of cells for banking and applications like high-throughput toxicity screening, scalable and robust methods need to be developed to enable the large-scale production of iPSCs. 3D suspension culture platforms are increasingly being used by stem cell researchers, owing to a higher cell output in a smaller footprint, as well as simpler scaling by increasing culture volume. Here we describe our strategies for successful scalable production of iPSCs using a benchtop bioreactor and incubator for 3D suspension cultures, while maintaining quality attributes expected of high-quality iPSC lines. Additionally, to meet the increasing demand for ready-to-use cell types, we report recent work to establish robust, scalable differentiation protocols to cardiac, neural, and hepatic fate to enable EBiSC to increase available research tools.

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