Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields
Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome t...
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Elsevier
2024-12-01
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| Series: | Mechanobiology in Medicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949907024000433 |
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| author | M. Ete Chan Christopher Ashdown Lia Strait Sishir Pasumarthy Abdullah Hassan Steven Crimarco Chanpreet Singh Vihitaben S. Patel Gabriel Pagnotti Omor Khan Gunes Uzer Clinton T. Rubin |
| author_facet | M. Ete Chan Christopher Ashdown Lia Strait Sishir Pasumarthy Abdullah Hassan Steven Crimarco Chanpreet Singh Vihitaben S. Patel Gabriel Pagnotti Omor Khan Gunes Uzer Clinton T. Rubin |
| author_sort | M. Ete Chan |
| collection | DOAJ |
| description | Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising – albeit less studied – physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1 g, 10–500 Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in Chinese Hamster Ovary (CHO)-adherent cells (+79% in 96 hr) using a particular set of LIV parameters (0.2 g, 500 Hz, 3 × 30 min/d, 2 hr refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (−13%). Another set of LIV parameters (30 Hz, 0.7 g, 2 × 60 min/d, 2 hr refractory period) however, were able to increase the proliferation of CHO-suspension cells by 210% and T-cells by 20.3%. Importantly, we also reported that T-cell response to LIV was in-part dependent upon AKT phosphorylation, as inhibiting AKT phosphorylation reduced the proliferative effect of LIV by over 60%, suggesting that suspension cells utilize mechanism(s) similar to adherent cells to sense specific LIV signals. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, it's highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges. |
| format | Article |
| id | doaj-art-a62f8df142764aeb8909d1b428636db7 |
| institution | Kabale University |
| issn | 2949-9070 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Mechanobiology in Medicine |
| spelling | doaj-art-a62f8df142764aeb8909d1b428636db72024-12-04T05:15:08ZengElsevierMechanobiology in Medicine2949-90702024-12-0124100080Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yieldsM. Ete Chan0Christopher Ashdown1Lia Strait2Sishir Pasumarthy3Abdullah Hassan4Steven Crimarco5Chanpreet Singh6Vihitaben S. Patel7Gabriel Pagnotti8Omor Khan9Gunes Uzer10Clinton T. Rubin11Department of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USADepartment of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USA; Medical Scientist Training Program, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794, USADepartment of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USADepartment of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USADepartment of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USADepartment of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USADepartment of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USADepartment of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USADepartment of Endocrine Neoplasia and Hormonal Disorders, MD Anderson Cancer Center, Houston, TX, 77030, USADepartment of Mechanical and Biomedical Engineering, College of Engineering, Boise State University, Boise, ID, 83725-205, USADepartment of Mechanical and Biomedical Engineering, College of Engineering, Boise State University, Boise, ID, 83725-205, USADepartment of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USA; Center for Biotechnology, New York State Center for Advanced Technology in Medical Biotechnology, Stony Brook University, Stony Brook, NY, 11794-5281, USA; Corresponding author. Rm 217, Stony Brook University, Stony Brook, NY, 11794-5281, USA.Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising – albeit less studied – physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1 g, 10–500 Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in Chinese Hamster Ovary (CHO)-adherent cells (+79% in 96 hr) using a particular set of LIV parameters (0.2 g, 500 Hz, 3 × 30 min/d, 2 hr refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (−13%). Another set of LIV parameters (30 Hz, 0.7 g, 2 × 60 min/d, 2 hr refractory period) however, were able to increase the proliferation of CHO-suspension cells by 210% and T-cells by 20.3%. Importantly, we also reported that T-cell response to LIV was in-part dependent upon AKT phosphorylation, as inhibiting AKT phosphorylation reduced the proliferative effect of LIV by over 60%, suggesting that suspension cells utilize mechanism(s) similar to adherent cells to sense specific LIV signals. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, it's highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.http://www.sciencedirect.com/science/article/pii/S2949907024000433BiomanufacturingCell proliferationMechanical stimulationBiomechanicsAdherent cellsSuspension cells |
| spellingShingle | M. Ete Chan Christopher Ashdown Lia Strait Sishir Pasumarthy Abdullah Hassan Steven Crimarco Chanpreet Singh Vihitaben S. Patel Gabriel Pagnotti Omor Khan Gunes Uzer Clinton T. Rubin Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields Mechanobiology in Medicine Biomanufacturing Cell proliferation Mechanical stimulation Biomechanics Adherent cells Suspension cells |
| title | Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields |
| title_full | Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields |
| title_fullStr | Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields |
| title_full_unstemmed | Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields |
| title_short | Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields |
| title_sort | low intensity mechanical signals promote proliferation in a cell specific manner tailoring a non drug strategy to enhance biomanufacturing yields |
| topic | Biomanufacturing Cell proliferation Mechanical stimulation Biomechanics Adherent cells Suspension cells |
| url | http://www.sciencedirect.com/science/article/pii/S2949907024000433 |
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