Determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervals
Abstract In regenerative medicine, mesenchymal stem cells (MSCs) constitute a promising therapeutic route for many diseases. The current quality-by-design guidelines do not clearly define a framework for MSC production. Here, we suggest and experimentally validate a model-based method to determine d...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08063-2 |
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| author | Keita Hirono Yusuke Hayashi Isuru A. Udugama Mohamed Rami Gaddem Kenjiro Tanaka Yuto Takemoto Ryuji Kato Masahiro Kino-oka Hirokazu Sugiyama |
| author_facet | Keita Hirono Yusuke Hayashi Isuru A. Udugama Mohamed Rami Gaddem Kenjiro Tanaka Yuto Takemoto Ryuji Kato Masahiro Kino-oka Hirokazu Sugiyama |
| author_sort | Keita Hirono |
| collection | DOAJ |
| description | Abstract In regenerative medicine, mesenchymal stem cells (MSCs) constitute a promising therapeutic route for many diseases. The current quality-by-design guidelines do not clearly define a framework for MSC production. Here, we suggest and experimentally validate a model-based method to determine design spaces (DSs) for MSC cultivation. A kinetic model used in previous work was employed; part of the experimental data was used to re-estimate the maximum specific growth rate in the kinetic model and then calculate the prediction intervals of this parameter. Subsequently, regions of seeding density and harvesting time where both the upper and lower limits of growth predictions met the acceptable number of cells and confluency with given risk levels were defined as DSs. Finally, the established DS was validated with the remaining data; it allowed better predictions of the cell numbers and confluency under specific cultivation conditions and improved the overall robustness of MSC cultivation processes. |
| format | Article |
| id | doaj-art-45d64a81a35f40acb36e57faf64135db |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-45d64a81a35f40acb36e57faf64135db2025-08-20T01:49:38ZengNature PortfolioCommunications Biology2399-36422025-05-018111210.1038/s42003-025-08063-2Determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervalsKeita Hirono0Yusuke Hayashi1Isuru A. Udugama2Mohamed Rami Gaddem3Kenjiro Tanaka4Yuto Takemoto5Ryuji Kato6Masahiro Kino-oka7Hirokazu Sugiyama8Department of Chemical System Engineering, The University of TokyoDepartment of Chemical System Engineering, The University of TokyoDepartment of Chemical System Engineering, The University of TokyoDepartment of Chemical System Engineering, The University of TokyoDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research SystemDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research SystemDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research SystemDepartment of Biotechnology, The University of OsakaDepartment of Chemical System Engineering, The University of TokyoAbstract In regenerative medicine, mesenchymal stem cells (MSCs) constitute a promising therapeutic route for many diseases. The current quality-by-design guidelines do not clearly define a framework for MSC production. Here, we suggest and experimentally validate a model-based method to determine design spaces (DSs) for MSC cultivation. A kinetic model used in previous work was employed; part of the experimental data was used to re-estimate the maximum specific growth rate in the kinetic model and then calculate the prediction intervals of this parameter. Subsequently, regions of seeding density and harvesting time where both the upper and lower limits of growth predictions met the acceptable number of cells and confluency with given risk levels were defined as DSs. Finally, the established DS was validated with the remaining data; it allowed better predictions of the cell numbers and confluency under specific cultivation conditions and improved the overall robustness of MSC cultivation processes.https://doi.org/10.1038/s42003-025-08063-2 |
| spellingShingle | Keita Hirono Yusuke Hayashi Isuru A. Udugama Mohamed Rami Gaddem Kenjiro Tanaka Yuto Takemoto Ryuji Kato Masahiro Kino-oka Hirokazu Sugiyama Determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervals Communications Biology |
| title | Determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervals |
| title_full | Determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervals |
| title_fullStr | Determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervals |
| title_full_unstemmed | Determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervals |
| title_short | Determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervals |
| title_sort | determination and validation of design space for mesenchymal stem cell cultivation processes using prediction intervals |
| url | https://doi.org/10.1038/s42003-025-08063-2 |
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