Xenogeneic-Free System for Biomanufacturing of Cardiomyocyte Progeny From Human Pluripotent Stem Cells
Functional heart cells and tissues sourced from human pluripotent stem cells (hPSCs) have great potential for substantially advancing treatments of cardiovascular maladies. Realization of this potential will require the development of cost-effective and tunable bioprocesses for manufacturing hPSC-ba...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2020.571425/full |
| _version_ | 1818286386461016064 |
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| author | Preeti Ashok Abhirath Parikh Chuang Du Emmanuel S. Tzanakakis Emmanuel S. Tzanakakis Emmanuel S. Tzanakakis |
| author_facet | Preeti Ashok Abhirath Parikh Chuang Du Emmanuel S. Tzanakakis Emmanuel S. Tzanakakis Emmanuel S. Tzanakakis |
| author_sort | Preeti Ashok |
| collection | DOAJ |
| description | Functional heart cells and tissues sourced from human pluripotent stem cells (hPSCs) have great potential for substantially advancing treatments of cardiovascular maladies. Realization of this potential will require the development of cost-effective and tunable bioprocesses for manufacturing hPSC-based cell therapeutics. Here, we report the development of a xeno-free platform for guiding the cardiogenic commitment of hPSCs. The system is based on a fully defined, open-source formulation without complex supplements, which have varied and often undetermined effects on stem cell physiology. The formulation was used to systematically investigate factors inducing the efficient commitment to cardiac mesoderm of three hPSC lines. Contractile clusters of cells appeared within a week of differentiation in planar cultures and by day 13 over 80% of the cells expressed cardiac progeny markers such as TNNT2. In conjunction with expansion, this differentiation strategy was employed in stirred-suspension cultures of hPSCs. Scalable differentiation resulted in 0.4–2 million CMs/ml or ∼5–20 TNNT2-positive cells per seeded hPSC without further enrichment. Our findings will contribute to the engineering of bioprocesses advancing the manufacturing of stem cell-based therapeutics for heart diseases. |
| first_indexed | 2024-12-13T01:23:46Z |
| format | Article |
| id | doaj.art-baa18fdc18394119a60cad340a361438 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-13T01:23:46Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-baa18fdc18394119a60cad340a3614382022-12-22T00:04:11ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-10-01810.3389/fbioe.2020.571425571425Xenogeneic-Free System for Biomanufacturing of Cardiomyocyte Progeny From Human Pluripotent Stem CellsPreeti Ashok0Abhirath Parikh1Chuang Du2Emmanuel S. Tzanakakis3Emmanuel S. Tzanakakis4Emmanuel S. Tzanakakis5Chemical and Biological Engineering, Tufts University, Medford, MA, United StatesKite Pharma, Gilead, Santa Monica, CA, United StatesBiomedical Engineering, Tufts University, Medford, MA, United StatesChemical and Biological Engineering, Tufts University, Medford, MA, United StatesClinical and Translational Science Institute, Tufts Medical Center, Boston, MA, United StatesDevelopmental Molecular and Chemical Biology, Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA, United StatesFunctional heart cells and tissues sourced from human pluripotent stem cells (hPSCs) have great potential for substantially advancing treatments of cardiovascular maladies. Realization of this potential will require the development of cost-effective and tunable bioprocesses for manufacturing hPSC-based cell therapeutics. Here, we report the development of a xeno-free platform for guiding the cardiogenic commitment of hPSCs. The system is based on a fully defined, open-source formulation without complex supplements, which have varied and often undetermined effects on stem cell physiology. The formulation was used to systematically investigate factors inducing the efficient commitment to cardiac mesoderm of three hPSC lines. Contractile clusters of cells appeared within a week of differentiation in planar cultures and by day 13 over 80% of the cells expressed cardiac progeny markers such as TNNT2. In conjunction with expansion, this differentiation strategy was employed in stirred-suspension cultures of hPSCs. Scalable differentiation resulted in 0.4–2 million CMs/ml or ∼5–20 TNNT2-positive cells per seeded hPSC without further enrichment. Our findings will contribute to the engineering of bioprocesses advancing the manufacturing of stem cell-based therapeutics for heart diseases.https://www.frontiersin.org/articles/10.3389/fbioe.2020.571425/fullhuman pluripotent stem cellscardiomyocytesbiomanufacturingxeno-free culturebioreactor |
| spellingShingle | Preeti Ashok Abhirath Parikh Chuang Du Emmanuel S. Tzanakakis Emmanuel S. Tzanakakis Emmanuel S. Tzanakakis Xenogeneic-Free System for Biomanufacturing of Cardiomyocyte Progeny From Human Pluripotent Stem Cells Frontiers in Bioengineering and Biotechnology human pluripotent stem cells cardiomyocytes biomanufacturing xeno-free culture bioreactor |
| title | Xenogeneic-Free System for Biomanufacturing of Cardiomyocyte Progeny From Human Pluripotent Stem Cells |
| title_full | Xenogeneic-Free System for Biomanufacturing of Cardiomyocyte Progeny From Human Pluripotent Stem Cells |
| title_fullStr | Xenogeneic-Free System for Biomanufacturing of Cardiomyocyte Progeny From Human Pluripotent Stem Cells |
| title_full_unstemmed | Xenogeneic-Free System for Biomanufacturing of Cardiomyocyte Progeny From Human Pluripotent Stem Cells |
| title_short | Xenogeneic-Free System for Biomanufacturing of Cardiomyocyte Progeny From Human Pluripotent Stem Cells |
| title_sort | xenogeneic free system for biomanufacturing of cardiomyocyte progeny from human pluripotent stem cells |
| topic | human pluripotent stem cells cardiomyocytes biomanufacturing xeno-free culture bioreactor |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2020.571425/full |
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