| NSF Org: |
TI Translational Impacts |
| Recipient: |
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| Initial Amendment Date: | January 25, 2022 |
| Latest Amendment Date: | December 29, 2023 |
| Award Number: | 2141019 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Jesus Soriano Molla
jsoriano@nsf.gov (703)292-7795 TI Translational Impacts TIP Directorate for Technology, Innovation, and Partnerships |
| Start Date: | February 1, 2022 |
| End Date: | December 31, 2023 (Estimated) |
| Total Intended Award Amount: | $250,000.00 |
| Total Awarded Amount to Date: | $266,000.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
360 HUNTINGTON AVE BOSTON MA US 02115-5005 (617)373-5600 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
MA US 02115-5005 |
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Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | PFI-Partnrships for Innovation |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.041, 47.084 |
ABSTRACT
The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is to enhance biomedical research by controlling oxygen in cell culture. Cell culture, in which scientists attempt to grow cells in conditions like those in the body, is one of the most useful techniques in biomedical research. However, oxygen, a critical factor for cell behavior and physiology, is not controlled during standard cell cultures. In fact, cells in laboratory cell culture experience up to 50-fold higher oxygen concentrations than they do in the body. By changing the status quo of cell culture from non-oxygen-controlled to oxygen-controlled, the proposed technology can advance the scientific understanding of oxygen?s role in disease development, biological processes, and human tissues. In addition, the technology can improve human health by (i) fueling the discovery of new drugs and drug targets, (ii) improving the accuracy of the drug screening process, reducing the attrition rate, cost and time spent on failed drugs, and (iii) accelerating the commercialization of cell-based therapies for cancer treatment and regenerative medicine.
The proposed project will develop the Oxygen-Controlling Cell Culture (OCC) system, an enzyme-based approach adaptable to the vessels already in use for cell culture. Unlike current oxygen-controlling products that function by reducing oxygen in the gas phase surrounding cell culture vessels, the OCC system takes an innovative approach by harnessing enzymes to locally control oxygen concentration directly in the cellular environment. This approach improves data accuracy, consistency, and reproducibility. The OCC system will be developed by testing a number of strategies to chemically attach enzymes to cell culture vessels. The oxygen concentration will be tuned to specific values by controlling the enzymatic depletion rates and oxygen transfer rates within the vessels. System performance will be validated by examining the impact on stem cells and cancer cell behavior and physiology. Through this proposal, it is anticipated that an OCC system prototype will be ready for the next stage of commercialization.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
Cell culture stands as one of the most widely employed techniques in biomedical research, aiming to cultivate cells under conditions mimicking their natural environment. However, conventional cell culture methods often overlook the control of oxygen (O2) levels. Through our participation in the NSF I-Corps Teams program, we recognized a significant demand and appreciation for O2 control in cell culture. Nonetheless, challenges related to reproducibility in O2-controlled cell culture pose a significant barrier. We discovered the primary cause of irreproducibility: cellular O2 consumption significantly impacts pericellular O2 tension, the concentration of O2 experienced by cells. For instance, we observed that physioxic (5% O2) and hypoxic (1% O2) conditions consistently lead to anoxic (~ 0% O2) pericellular O2 tensions in both adherent and suspension cell cultures. To address this challenge, we devised computational and experimental strategies to enhance O2 control, resulting in a novel approach named pericellular O2-controlled cell culture. Using this method, we demonstrated that breast cancer responses to pericellular hypoxia (1% O2) and anoxia (~ 0% O2) are fundamentally different, suggesting that anoxia is not suitable to model hypoxia. This endeavor also provided valuable scientific training to graduate student Zachary Rogers, who successfully defended his PhD in November 2023. In summary, our findings underscore the inadequacy of current O2-controlled cell culture methods in accurately regulating O2. Our pericellular control method addresses this challenge, potentially establishing O2-controlled cell culture as the standard practice in biomedical research.
Last Modified: 02/29/2024
Modified by: Sidi A Bencherif
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