Inverse problem analysis of pluripotent stem cell aggregation dynamics in stirred-suspension cultures.
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| Title: | Inverse problem analysis of pluripotent stem cell aggregation dynamics in stirred-suspension cultures. |
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| Authors: | Rostami, Mahboubeh Rahmati1 mahboubeh@tufts.edu, Wu, Jincheng1 jincheng.wu@tufts.edu, Tzanakakis, Emmanuel S.1,2 Tzanakakis@tufts.edu |
| Source: | Journal of Biotechnology. Aug2015, Vol. 208, p70-79. 10p. |
| Subjects: | Pluripotent stem cells, Bioreactors, Biological aggregation, Embryonic stem cells, Regenerative medicine, Drug use testing |
| Abstract: | The cultivation of stem cells as aggregates in scalable bioreactor cultures is an appealing modality for the large-scale manufacturing of stem cell products. Aggregation phenomena are central to such bioprocesses affecting the viability, proliferation and differentiation trajectory of stem cells but a quantitative framework is currently lacking. A population balance equation (PBE) model was used to describe the temporal evolution of the embryonic stem cell (ESC) cluster size distribution by considering collision-induced aggregation and cell proliferation in a stirred-suspension vessel. For ESC cultures at different agitation rates, the aggregation kernel representing the aggregation dynamics was successfully recovered as a solution of the inverse problem. The rate of change of the average aggregate size was greater at the intermediate rate tested suggesting a trade-off between increased collisions and agitation-induced shear. Results from forward simulation with obtained aggregation kernels were in agreement with transient aggregate size data from experiments. We conclude that the framework presented here can complement mechanistic studies offering insights into relevant stem cell clustering processes. More importantly from a process development standpoint, this strategy can be employed in the design and control of bioreactors for the generation of stem cell derivatives for drug screening, tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biotechnology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 103425334 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Inverse problem analysis of pluripotent stem cell aggregation dynamics in stirred-suspension cultures. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Rostami%2C+Mahboubeh+Rahmati%22">Rostami, Mahboubeh Rahmati</searchLink><relatesTo>1</relatesTo><i> mahboubeh@tufts.edu</i><br /><searchLink fieldCode="AR" term="%22Wu%2C+Jincheng%22">Wu, Jincheng</searchLink><relatesTo>1</relatesTo><i> jincheng.wu@tufts.edu</i><br /><searchLink fieldCode="AR" term="%22Tzanakakis%2C+Emmanuel+S%2E%22">Tzanakakis, Emmanuel S.</searchLink><relatesTo>1,2</relatesTo><i> Tzanakakis@tufts.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biotechnology%22">Journal of Biotechnology</searchLink>. Aug2015, Vol. 208, p70-79. 10p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Pluripotent+stem+cells%22">Pluripotent stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22Bioreactors%22">Bioreactors</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+aggregation%22">Biological aggregation</searchLink><br /><searchLink fieldCode="DE" term="%22Embryonic+stem+cells%22">Embryonic stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22Regenerative+medicine%22">Regenerative medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+use+testing%22">Drug use testing</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The cultivation of stem cells as aggregates in scalable bioreactor cultures is an appealing modality for the large-scale manufacturing of stem cell products. Aggregation phenomena are central to such bioprocesses affecting the viability, proliferation and differentiation trajectory of stem cells but a quantitative framework is currently lacking. A population balance equation (PBE) model was used to describe the temporal evolution of the embryonic stem cell (ESC) cluster size distribution by considering collision-induced aggregation and cell proliferation in a stirred-suspension vessel. For ESC cultures at different agitation rates, the aggregation kernel representing the aggregation dynamics was successfully recovered as a solution of the inverse problem. The rate of change of the average aggregate size was greater at the intermediate rate tested suggesting a trade-off between increased collisions and agitation-induced shear. Results from forward simulation with obtained aggregation kernels were in agreement with transient aggregate size data from experiments. We conclude that the framework presented here can complement mechanistic studies offering insights into relevant stem cell clustering processes. More importantly from a process development standpoint, this strategy can be employed in the design and control of bioreactors for the generation of stem cell derivatives for drug screening, tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biotechnology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.jbiotec.2015.05.018 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 70 Subjects: – SubjectFull: Pluripotent stem cells Type: general – SubjectFull: Bioreactors Type: general – SubjectFull: Biological aggregation Type: general – SubjectFull: Embryonic stem cells Type: general – SubjectFull: Regenerative medicine Type: general – SubjectFull: Drug use testing Type: general Titles: – TitleFull: Inverse problem analysis of pluripotent stem cell aggregation dynamics in stirred-suspension cultures. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Rostami, Mahboubeh Rahmati – PersonEntity: Name: NameFull: Wu, Jincheng – PersonEntity: Name: NameFull: Tzanakakis, Emmanuel S. IsPartOfRelationships: – BibEntity: Dates: – D: 20 M: 08 Text: Aug2015 Type: published Y: 2015 Identifiers: – Type: issn-print Value: 01681656 Numbering: – Type: volume Value: 208 Titles: – TitleFull: Journal of Biotechnology Type: main |
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