Mass production of iPSC-derived platelets toward the clinical application
The ex vivo production of platelets from induced pluripotent cells (iPSCs) may offer a safer and sustainable alternative for transfusions and drug delivery systems (DDS). However, the mass production of the clinically required number of iPSC-derived platelets (iPSC-PLTs) is challenging. Here, we int...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320423001426 |
| _version_ | 1797268973907083264 |
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| author | Akihiro Kayama Koji Eto |
| author_facet | Akihiro Kayama Koji Eto |
| author_sort | Akihiro Kayama |
| collection | DOAJ |
| description | The ex vivo production of platelets from induced pluripotent cells (iPSCs) may offer a safer and sustainable alternative for transfusions and drug delivery systems (DDS). However, the mass production of the clinically required number of iPSC-derived platelets (iPSC-PLTs) is challenging. Here, we introduce recent technologies for mass production and the first-in-human clinical trial using ex vivo iPSC-PLTs. To this end, we established immortalized megakaryocyte progenitor cell lines (imMKCLs) as an expandable master cell bank (MCB) through the overexpression of c-MYC, BMI1 and BCL-XL, which modulated megakaryopoiesis and thrombopoiesis. We also optimized a culture cocktail for maturation of the imMKCLs by mixing an aryl hydrocarbon receptor (AhR) antagonist, SR1/GNF-316; a Rho-associated protein kinase (ROCK) inhibitor, Y-27632/Y-39983; and a small-molecule compound replacing recombinant thrombopoietin (TPO), TA-316. Finally, we discovered the importance of turbulence on the manufacturing of intact iPSC-PLTs, allowing us to develop a turbulence-based bioreactor, VerMES. Combination of the MCB and VerMES enabled us to produce more than 100 billion iPSC-PLTs, leading to the first-in-human clinical trial. Despite these advancements, many challenges remain before expanding the clinical implementation of this strategy. |
| first_indexed | 2024-03-08T16:50:59Z |
| format | Article |
| id | doaj.art-585b1efe4b804822a515f4194e87a60f |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2024-04-25T01:41:00Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-585b1efe4b804822a515f4194e87a60f2024-03-08T05:18:47ZengElsevierRegenerative Therapy2352-32042024-03-0125213219Mass production of iPSC-derived platelets toward the clinical applicationAkihiro Kayama0Koji Eto1Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shōgoin Kawarachō, Sakyo Ward, Kyoto, 606-8397, JapanCorresponding author.; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shōgoin Kawarachō, Sakyo Ward, Kyoto, 606-8397, JapanThe ex vivo production of platelets from induced pluripotent cells (iPSCs) may offer a safer and sustainable alternative for transfusions and drug delivery systems (DDS). However, the mass production of the clinically required number of iPSC-derived platelets (iPSC-PLTs) is challenging. Here, we introduce recent technologies for mass production and the first-in-human clinical trial using ex vivo iPSC-PLTs. To this end, we established immortalized megakaryocyte progenitor cell lines (imMKCLs) as an expandable master cell bank (MCB) through the overexpression of c-MYC, BMI1 and BCL-XL, which modulated megakaryopoiesis and thrombopoiesis. We also optimized a culture cocktail for maturation of the imMKCLs by mixing an aryl hydrocarbon receptor (AhR) antagonist, SR1/GNF-316; a Rho-associated protein kinase (ROCK) inhibitor, Y-27632/Y-39983; and a small-molecule compound replacing recombinant thrombopoietin (TPO), TA-316. Finally, we discovered the importance of turbulence on the manufacturing of intact iPSC-PLTs, allowing us to develop a turbulence-based bioreactor, VerMES. Combination of the MCB and VerMES enabled us to produce more than 100 billion iPSC-PLTs, leading to the first-in-human clinical trial. Despite these advancements, many challenges remain before expanding the clinical implementation of this strategy.http://www.sciencedirect.com/science/article/pii/S2352320423001426iPS cellsPlateletsTurbulenceShear stressBioreactorTransfusion |
| spellingShingle | Akihiro Kayama Koji Eto Mass production of iPSC-derived platelets toward the clinical application Regenerative Therapy iPS cells Platelets Turbulence Shear stress Bioreactor Transfusion |
| title | Mass production of iPSC-derived platelets toward the clinical application |
| title_full | Mass production of iPSC-derived platelets toward the clinical application |
| title_fullStr | Mass production of iPSC-derived platelets toward the clinical application |
| title_full_unstemmed | Mass production of iPSC-derived platelets toward the clinical application |
| title_short | Mass production of iPSC-derived platelets toward the clinical application |
| title_sort | mass production of ipsc derived platelets toward the clinical application |
| topic | iPS cells Platelets Turbulence Shear stress Bioreactor Transfusion |
| url | http://www.sciencedirect.com/science/article/pii/S2352320423001426 |
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