Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling
Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) hold great potential to generate novel and curative cell therapy products. However, the current large-scale cultivation of hUCMSCs is based on empirical geometry-dependent methods, limiting the generation of high-quantity and high-quality...
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MDPI AG
2022-06-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/9/7/274 |
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| author | Junhong Zhang Yan Peng Meijin Guo Chao Li |
| author_facet | Junhong Zhang Yan Peng Meijin Guo Chao Li |
| author_sort | Junhong Zhang |
| collection | DOAJ |
| description | Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) hold great potential to generate novel and curative cell therapy products. However, the current large-scale cultivation of hUCMSCs is based on empirical geometry-dependent methods, limiting the generation of high-quantity and high-quality hUCMSCs for clinical therapy. Herein, we develop a novel scale-up strategy based on computational fluid dynamics (CFD) to effectively expand the hUCMSCs in a 3D tank bioreactor. Using a standardized hUCMSCs line on microcarriers, we successfully translated and expanded the hUCMSCs from a 200 mL spinner flask to a 1.5 L computer-controlled bioreactor by matching the shear environment and suspending the microcarrier. Experimental results revealed that the batch-cultured hUCMSCs in bioreactors with an agitation speed of 40 rpm shared a more favorable growth and physiological state, similar to that run at 45 rpm in a 200 mL spinner flask, showing comparability in both culture systems. Notably, the maximum cell density reached up to 27.3 × 10<sup>5</sup> cells/mL in fed-batch culture, 2.9 folds of that of batch culture and 20.2 times of seeding cells. As such, efficient process optimization and scale-up expansion of hUCMSCs were achieved in the microcarrier-based bioreactor system by the developed CFD simulation strategy, which provided an alternative toolbox to generate massive and standardized curative cell therapy products. |
| first_indexed | 2024-03-09T03:41:12Z |
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| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-09T03:41:12Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
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| series | Bioengineering |
| spelling | doaj.art-1ce27b87b37446f2ad8208864434a3472023-12-03T14:39:31ZengMDPI AGBioengineering2306-53542022-06-019727410.3390/bioengineering9070274Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics ModelingJunhong Zhang0Yan Peng1Meijin Guo2Chao Li3State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Rd., Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Rd., Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Rd., Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Rd., Shanghai 200237, ChinaHuman umbilical cord-derived mesenchymal stem cells (hUCMSCs) hold great potential to generate novel and curative cell therapy products. However, the current large-scale cultivation of hUCMSCs is based on empirical geometry-dependent methods, limiting the generation of high-quantity and high-quality hUCMSCs for clinical therapy. Herein, we develop a novel scale-up strategy based on computational fluid dynamics (CFD) to effectively expand the hUCMSCs in a 3D tank bioreactor. Using a standardized hUCMSCs line on microcarriers, we successfully translated and expanded the hUCMSCs from a 200 mL spinner flask to a 1.5 L computer-controlled bioreactor by matching the shear environment and suspending the microcarrier. Experimental results revealed that the batch-cultured hUCMSCs in bioreactors with an agitation speed of 40 rpm shared a more favorable growth and physiological state, similar to that run at 45 rpm in a 200 mL spinner flask, showing comparability in both culture systems. Notably, the maximum cell density reached up to 27.3 × 10<sup>5</sup> cells/mL in fed-batch culture, 2.9 folds of that of batch culture and 20.2 times of seeding cells. As such, efficient process optimization and scale-up expansion of hUCMSCs were achieved in the microcarrier-based bioreactor system by the developed CFD simulation strategy, which provided an alternative toolbox to generate massive and standardized curative cell therapy products.https://www.mdpi.com/2306-5354/9/7/274UC-mesenchymal stem cellsscale-up expansioncomputational fluid dynamicsmicrocarrier-based bioreactorsthree-dimensional suspension culture |
| spellingShingle | Junhong Zhang Yan Peng Meijin Guo Chao Li Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling Bioengineering UC-mesenchymal stem cells scale-up expansion computational fluid dynamics microcarrier-based bioreactors three-dimensional suspension culture |
| title | Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling |
| title_full | Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling |
| title_fullStr | Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling |
| title_full_unstemmed | Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling |
| title_short | Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling |
| title_sort | large scale expansion of human umbilical cord derived mesenchymal stem cells in a stirred suspension bioreactor enabled by computational fluid dynamics modeling |
| topic | UC-mesenchymal stem cells scale-up expansion computational fluid dynamics microcarrier-based bioreactors three-dimensional suspension culture |
| url | https://www.mdpi.com/2306-5354/9/7/274 |
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