The StemCellFactory: A Modular System Integration for Automated Generation and Expansion of Human Induced Pluripotent Stem Cells

Elanzew, Andreas; Nießing, Bastian; Langendoerfer, Daniel; Rippel, Oliver; Piotrowski, Tobias; Schenk, Friedrich; Kulik, Michael; Peitz, Michael; Breitkreuz, Yannik; Jung, Sven; Wanek, Paul; Stappert, Laura; Schmitt, Robert; Haupt, Simone; Zenke, Martin; König, Niels; Brüstle, Oliver

doi:10.3389/fbioe.2020.580352

Cited by 31 publications

(30 citation statements)

References 42 publications

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“…However, expanding this technology to whole patient cohorts will require the application of automation systems to reduce the manpower, timescale, and cost associated with deriving lines from multiple patients. This process is underway in our group as well as in other laboratories [54][55][56].…”

Section: Discussionmentioning

confidence: 88%

Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration

et al. 2022

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Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or “dry” AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies provide evidence for the involvement of mitochondrial dysfunction in AMD pathology. This study used induced pluripotent stem cell (iPSC) RPE derived from five AMD patients to test the efficacy of three drugs (AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), Metformin, trehalose) that target key processes in maintaining optimal mitochondrial function. The patient iPSC-RPE lines were used in a proof-of-concept drug screen, utilizing an analysis of RPE mitochondrial function following acute and extended drug exposure. Results show considerable variability in drug response across patient cell lines, supporting the need for a personalized medicine approach for treating AMD. Furthermore, our results demonstrate the feasibility of using iPSC-RPE from AMD patients to develop a personalized drug treatment regime and provide a roadmap for the future clinical management of AMD.

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Section: Discussionmentioning

confidence: 88%

Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration

et al. 2022

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“…This does not only require performant imaging systems such as the high-speed microscope described by Schenk et al [19] but also image processing algorithms capable of translating the image into meaningful information. Such an approach was first introduced into the StemCellFactory, a fully robotic laboratory for the production of iPSCs [31]. Here, we introduced a deep learning-based image processing approach for detection of hMSCs.…”

Section: Discussionmentioning

confidence: 99%

Fully Automated Cultivation of Adipose-Derived Stem Cells in the StemCellDiscovery—A Robotic Laboratory for Small-Scale, High-Throughput Cell Production Including Deep Learning-Based Confluence Estimation

et al. 2021

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Laboratory automation is a key driver in biotechnology and an enabler for powerful new technologies and applications. In particular, in the field of personalized therapies, automation in research and production is a prerequisite for achieving cost efficiency and broad availability of tailored treatments. For this reason, we present the StemCellDiscovery, a fully automated robotic laboratory for the cultivation of human mesenchymal stem cells (hMSCs) in small scale and in parallel. While the system can handle different kinds of adherent cells, here, we focus on the cultivation of adipose-derived hMSCs. The StemCellDiscovery provides an in-line visual quality control for automated confluence estimation, which is realized by combining high-speed microscopy with deep learning-based image processing. We demonstrate the feasibility of the algorithm to detect hMSCs in culture at different densities and calculate confluences based on the resulting image. Furthermore, we show that the StemCellDiscovery is capable of expanding adipose-derived hMSCs in a fully automated manner using the confluence estimation algorithm. In order to estimate the system capacity under high-throughput conditions, we modeled the production environment in a simulation software. The simulations of the production process indicate that the robotic laboratory is capable of handling more than 95 cell culture plates per day.

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“…Figure 1 shows the general process of cell cultivation. The StemCellFactory (SCF) is a prototype for such a fully automated production of iPSC [12]. The automation and parallelization of the handling processes makes it possible to reproduce iPSC-lines.…”

Section: Manual Ipsc Production Processmentioning

confidence: 99%

“…Using the SCF platform as shown in Figure 2, it is possible to automate this complex process and it was shown to allow for undifferentiated iPSC cultivation [12]. The SCF platform was equipped by the Fraunhofer Institute for Production Technology (IPT) with processing, analysis and storage modules The integrated equipment includes the essential incubators in which the iPSC and all other cells grow (I), a microscope for daily visual examination of the cells (II), a plate reader for turbidity-based detection of bacterial contamination (III), a material gate for the controlled loading and storage of consumables (IV) and a liquid handling unit (LHU) for performing the various pipetting operations (V).…”

Section: Need For Automated Ipsc Productionmentioning

confidence: 99%

“…Static methods assume constant payments and earnings and do not take the changing actual cash value or the time of investments into account. The main advantage of the static method over the dynamic method therefore is the simplicity of the calculation method [11,12]. In theory, it is mainly distinguished between four methods to statically analyze the economic efficiency.…”

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confidence: 99%

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Techno-Economic Analysis of Automated iPSC Production

et al. 2021

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Induced pluripotent stem cells (iPSC) open up the unique perspective of manufacturing cell products for drug development and regenerative medicine in tissue-, disease- and patient-specific forms. iPSC can be multiplied almost without restriction and differentiated into cell types of all organs. The basis for clinical use of iPSC is a high number of cells (approximately 7 × 107 cells per treatment), which must be produced cost-effectively while maintaining reproducible and high quality. Compared to manual cell production, the automation of cell production offers a unique chance of reliable reproducibility of cells in addition to cost reduction and increased throughput. StemCellFactory is a prototype for a fully automated production of iPSC. However, in addition to the already tested functionality of the system, it must be shown that this automation brings necessary economic advantages. This paper presents that fully automated stem cell production offers economic advantages in addition to increased throughput and better quality. First, biological and technological basics for a fully automated production of iPSC are presented. Second, the basics for profitability calculation are presented. Third, profitability of both manual and automated production are calculated. Finally, different scenarios effecting the profitability of manual and automated production are compared.

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The StemCellFactory: A Modular System Integration for Automated Generation and Expansion of Human Induced Pluripotent Stem Cells

Cited by 31 publications

References 42 publications

Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration

Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration

Fully Automated Cultivation of Adipose-Derived Stem Cells in the StemCellDiscovery—A Robotic Laboratory for Small-Scale, High-Throughput Cell Production Including Deep Learning-Based Confluence Estimation

Techno-Economic Analysis of Automated iPSC Production

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