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Project Title:  Study of Mammalian Pluripotent Stem Cells in Microgravity Expand All
Images: icon  Fiscal Year: FY 2018 
Division: Space Biology 
Research Discipline/Element:
Cell & Molecular Biology 
Start Date: 11/01/2014  
End Date: 11/01/2019  
Task Last Updated: 05/24/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hammer, Bruce  Ph.D. / University of Minnesota 
Address:  Radiology Department 
2021 6th St SE 
Minneapolis , MN 55455-3007 
Email: hammer@umn.edu 
Phone: 612-624-5641  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Minnesota 
Comments:  
Co-Investigator(s) / Affiliation:  Dutton, James  Ph.D./ University of Minnesota  Kidder, Louis  Ph.D./ University of Minnesota 
Project Information: Grant/Contract No. NNX15AB38G 
Responsible Center: NASA ARC 
Grant Monitor: Sato, Kevin  
Center Contact: 650-604-1104 
kevin.y.sato@nasa.gov 
Solicitation: 2014 Space Biology Flight NNH14ZTT001N 
Grant/Contract No.: NNX15AB38G 
Project Type: FLIGHT  
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Space Biology Element: (1) Cell & Molecular Biology
Space Biology Cross-Element Discipline: (1) Developmental Biology
Space Biology Special Category: (1) Cell Culture
Task Description: We propose to investigate the effect of gravity on fundamental properties of mammalian stem cells during differentiation of 3-D cultures of induced pluripotent stem (iPS) cells. Experiments aboard the ISS (International Space Station), STS (Shuttle), and ground-based simulations have demonstrated that microgravity influences gene expression, cell proliferation, and differentiation in stem cells. However, the mechanism behind these observations is not clearly understood. In this study we will investigate how exposure to microgravity fundamentally alters the regulation of Oct4, a transcription factor necessary to maintain pluripotency, and how these changes can affect the timing, progression, and outcomes of cell differentiation. Our laboratory has created an Oct4:CreER mTmG transgenic mouse that, for the first time, allows lineage tracing of Oct4 expression in stem cells and their progeny. We will use iPS cells derived from this model to determine the influence of microgravity on the loss of pluripotency and differentiation.

During the Flight Definition Phase we will use magnetic levitation, a unique ground-based simulation of orbital free fall, to optimize execution of the Spaceflight Experiment Phase. This approach will maximize the success of space-based studies. We propose to investigate the effect of gravity on the timing and spatial arrangement of the loss of Oct4 expression in differentiating iPS cell aggregates. We will also examine the effect of gravity on gene expression in cohorts of Oct4 expressing and non-expressing cells during differentiation by comparing the results of ground-based experiments to those conducted on orbit. Finally, we will explore mechanisms behind the effect of microgravity on both Oct4 gene regulation and control of downstream gene expression by Oct4. This work will determine the effect of spaceflight on changes in Oct4 gene expression during differentiation of pluripotent stem cells and the consequences of these changes on differentiation outcomes. This will increase our understanding of fundamental stem cell behavior in microgravity.

 

Flight Assignment/Project Notes: NOTE: Extended to 11/1/2019 per F. Hernandez/ARC (Ed., 11/6/18)

NOTE: Extended to 11/1/2018 per F. Hernandez/ARC (Ed., 10/21/16)

 

Research Impact/Earth Benefits: Gravity likely influences organismal development but little is currently understood about its specific influence on stem cell differentiation. We propose to utilize a novel system to investigate how microgravity fundamentally changes the timing and spatial arrangement of the loss of Oct4 gene expression during the differentiation of stem cells. We expect this to have consequences on differentiation outcomes. Our results from this study will ultimately have a direct impact on improving the translation of human stem cell based treatments. Cell manufacturing in microgravity may speed-up the rate of iPSC (induced Pluripotency Stem Cell) differentiation, thereby reducing the time and cost to obtain a therapeutic dose of cells. If this can be done on-orbit and replicated on Earth with magnetic levitation, this will have significant commercialization possibilities.

 

Task Progress & Bibliography Information FY2018 
Task Progress: Due to delays in obtaining crew time aboard the ISS we have postponed full start of project to conserve resources. The flight definition plan was approved in year 1 and placed on temporary hold from January 2016 until January 2018 when ISS crew time was approved for the project. The first phase of the project focused on generating embryoid bodies (EBs) which are 200 micron spherical aggregates of iPSCs (induced Pluripotent Stem Cells) and developing freezing protocols so that EBs can be transported and stored at -95 C aboard the ISS until crew time is allocated to the project. We determined that EBs did not cryopreserve well and investigated the possibility of previously frozen stem cells self-assembling into EBs aboard the ISS. This procedure has been done successfully in a conventional incubator (1g) and when exposed to simulated microgravity via magnetic levitation in our laboratory. These self-aggregated EBs exhibit the same fluorescence patterns when tamoxifen treated as those grown on 96 well plates. A significant benefit of transporting frozen stem cells to the ISS for self-assembly avoids g-force and vibration of launch as well as ground and berthing delays which can damage fragile stem cells.

 

Bibliography Type: Description: (Last Updated: )  Show Cumulative Bibliography Listing
 
 None in FY 2018
Project Title:  Study of Mammalian Pluripotent Stem Cells in Microgravity Expand All
Images: icon  Fiscal Year: FY 2017 
Division: Space Biology 
Research Discipline/Element:
Cell & Molecular Biology 
Start Date: 11/01/2014  
End Date: 11/01/2018  
Task Last Updated: 10/18/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hammer, Bruce  Ph.D. / University of Minnesota 
Address:  Radiology Department 
2021 6th St SE 
Minneapolis , MN 55455-3007 
Email: hammer@umn.edu 
Phone: 612-624-5641  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Minnesota 
Comments:  
Co-Investigator(s) / Affiliation:  Dutton, James  Ph.D./ University of Minnesota  Kidder, Louis  Ph.D./ University of Minnesota 
Project Information: Grant/Contract No. NNX15AB38G 
Responsible Center: NASA ARC 
Grant Monitor: Sato, Kevin  
Center Contact: 650-604-1104 
kevin.y.sato@nasa.gov 
Solicitation: 2014 Space Biology Flight NNH14ZTT001N 
Grant/Contract No.: NNX15AB38G 
Project Type: FLIGHT  
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Space Biology Element: (1) Cell & Molecular Biology
Space Biology Cross-Element Discipline: (1) Developmental Biology
Space Biology Special Category: (1) Cell Culture
Task Description: We propose to investigate the effect of gravity on fundamental properties of mammalian stem cells during differentiation of 3-D cultures of induced pluripotent stem (iPS) cells. Experiments aboard the ISS (International Space Station), STS (Shuttle), and ground-based simulations have demonstrated that microgravity influences gene expression, cell proliferation, and differentiation in stem cells. However, the mechanism behind these observations is not clearly understood. In this study we will investigate how exposure to microgravity fundamentally alters the regulation of Oct4, a transcription factor necessary to maintain pluripotency, and how these changes can affect the timing, progression, and outcomes of cell differentiation. Our laboratory has created an Oct4:CreER mTmG transgenic mouse that, for the first time, allows lineage tracing of Oct4 expression in stem cells and their progeny. We will use iPS cells derived from this model to determine the influence of microgravity on the loss of pluripotency and differentiation.

During the Flight Definition Phase we will use magnetic levitation, a unique ground-based simulation of orbital free fall, to optimize execution of the Spaceflight Experiment Phase. This approach will maximize the success of space-based studies. We propose to investigate the effect of gravity on the timing and spatial arrangement of the loss of Oct4 expression in differentiating iPS cell aggregates. We will also examine the effect of gravity on gene expression in cohorts of Oct4 expressing and non-expressing cells during differentiation by comparing the results of ground-based experiments to those conducted on orbit. Finally, we will explore mechanisms behind the effect of microgravity on both Oct4 gene regulation and control of downstream gene expression by Oct4. This work will determine the effect of spaceflight on changes in Oct4 gene expression during differentiation of pluripotent stem cells and the consequences of these changes on differentiation outcomes. This will increase our understanding of fundamental stem cell behavior in microgravity.

 

Flight Assignment/Project Notes: NOTE: Extended to 11/1/2018 per F. Hernandez/ARC (Ed., 10/21/16)

 

Research Impact/Earth Benefits: Gravity likely influences organismal development but little is currently understood about its specific influence on stem cell differentiation. We propose to utilize a novel system to investigate how microgravity fundamentally changes the timing and spatial arrangement of the loss of Oct4 gene expression during the differentiation of stem cells. We expect this to have consequences on differentiation outcomes. Our results from this study will ultimately have a direct impact on improving the translation of human stem cell based treatments. Cell manufacturing in microgravity may speed-up the rate of iPSC (induced Pluripotency Stem Cell) differentiation, thereby reducing the time and cost to obtain a therapeutic dose of cells. If this can be done on-orbit and replicated on Earth with magnetic levitation, this will have significant commercialization possibilities.

 

Task Progress & Bibliography Information FY2017 
Task Progress: Due to delays in obtaining crew time aboard the ISS we have postponed full start of project to conserve resources. Due to the translational nature of our proposed work and in an effort to acquire more ISS resources (including crew time), we submitted an ISSNL Co-Sponsorship Request Document between NASA and CASIS (Center for the Advancement of Science in Space) in August 2015 and are awaiting the outcome of the application. The flight definition plan was approved in year 1 and placed on temporary hold from January 2016 until July 2016. The first phase of the project (start date July 2016) focuses on generating embryoid bodies (EBs) and developing freezing protocols so that EBs can be transported and stored at -95 degrees C aboard the ISS until crew time is allocated to the project. Another benefit of transporting frozen EBs to the ISS is to avoid g-force and vibration of launch as well as ground and berthing delays which can damage fragile EBs.

 

Bibliography Type: Description: (Last Updated: )  Show Cumulative Bibliography Listing
 
 None in FY 2017
Project Title:  Study of Mammalian Pluripotent Stem Cells in Microgravity Expand All
Images: icon  Fiscal Year: FY 2016 
Division: Space Biology 
Research Discipline/Element:
Cell & Molecular Biology 
Start Date: 11/01/2014  
End Date: 10/31/2016  
Task Last Updated: 02/20/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hammer, Bruce  Ph.D. / University of Minnesota 
Address:  Radiology Department 
2021 6th St SE 
Minneapolis , MN 55455-3007 
Email: hammer@umn.edu 
Phone: 612-624-5641  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Minnesota 
Comments:  
Co-Investigator(s) / Affiliation:  Dutton, James  Ph.D./ University of Minnesota  Kidder, Louis  Ph.D./ University of Minnesota 
Project Information: Grant/Contract No. NNX15AB38G 
Responsible Center: NASA ARC 
Grant Monitor: Taylor, Elizabeth  
Center Contact: 650.604.1783 
elizabeth.taylor-23@nasa.gov 
Solicitation: 2014 Space Biology Flight NNH14ZTT001N 
Grant/Contract No.: NNX15AB38G 
Project Type: FLIGHT  
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Space Biology Element: (1) Cell & Molecular Biology
Space Biology Cross-Element Discipline: (1) Developmental Biology
Space Biology Special Category: (1) Cell Culture
Task Description: We propose to investigate the effect of gravity on fundamental properties of mammalian stem cells during differentiation of 3-D cultures of induced pluripotent stem (iPS) cells. Experiments aboard the ISS (International Space Station), STS, and ground-based simulations have demonstrated that microgravity influences gene expression, cell proliferation, and differentiation in stem cells. However, the mechanism behind these observations is not clearly understood. In this study we will investigate how exposure to microgravity fundamentally alters the regulation of Oct4, a transcription factor necessary to maintain pluripotency, and how these changes can affect the timing, progression, and outcomes of cell differentiation. Our laboratory has created an Oct4:CreER mTmG transgenic mouse that, for the first time, allows lineage tracing of Oct4 expression in stem cells and their progeny. We will use iPS cells derived from this model to determine the influence of microgravity on the loss of pluripotency and differentiation.

During the Flight Definition Phase we will use magnetic levitation, a unique ground-based simulation of orbital free fall, to optimize execution of the Spaceflight Experiment Phase. This approach will maximize the success of space-based studies. We propose to investigate the effect of gravity on the timing and spatial arrangement of the loss of Oct4 expression in differentiating iPS cell aggregates. We will also examine the effect of gravity on gene expression in cohorts of Oct4 expressing and non-expressing cells during differentiation by comparing the results of ground-based experiments to those conducted on orbit. Finally, we will explore mechanisms behind the effect of microgravity on both Oct4 gene regulation and control of downstream gene expression by Oct4. This work will determine the effect of spaceflight on changes in Oct4 gene expression during differentiation of pluripotent stem cells and the consequences of these changes on differentiation outcomes. This will increase our understanding of fundamental stem cell behavior in microgravity.

 

Research Impact/Earth Benefits: Gravity likely influences organismal development but little is currently understood about its specific influence on stem cell differentiation. We propose to utilize a novel system to investigate how microgravity fundamentally changes the timing and spatial arrangement of the loss of Oct4 gene expression during the differentiation of stem cells. We expect this to have consequences on differentiation outcomes. Our results from this study will ultimately have a direct impact on improving the translation of human stem cell based treatments. Cell manufacturing in microgravity may speed-up the rate of iPSC (induced Pluripotency Stem Cell) differentiation, thereby reducing the time and cost to obtain a therapeutic dose of cells. If this can be done on-orbit and replicated on Earth with magnetic levitation, this will have significant commercialization possibilities.

 

Task Progress & Bibliography Information FY2016 
Task Progress: Due to a delay in funding of the project we have postponed the full start of work. During this time we have completed the Flight Definition Plan. This was presented to NASA Headquarters and NASA Ames in June 2015. The plan was approved and we are on hold until funding of the project commences. Due to the translational nature of our proposed work and in an effort to acquire more ISS resources (including crew time), we submitted an ISSNL Co-sponsorship Request Document between NASA and CASIS (Center for the Advancement of Science in Space) in August 2015 and are awaiting the outcome of the application.

 

Bibliography Type: Description: (Last Updated: )  Show Cumulative Bibliography Listing
 
 None in FY 2016
Project Title:  Study of Mammalian Pluripotent Stem Cells in Microgravity Expand All
Images: icon  Fiscal Year: FY 2015 
Division: Space Biology 
Research Discipline/Element:
Cell & Molecular Biology 
Start Date: 11/01/2014  
End Date: 10/31/2016  
Task Last Updated: 11/24/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hammer, Bruce  Ph.D. / University of Minnesota 
Address:  Radiology Department 
2021 6th St SE 
Minneapolis , MN 55455-3007 
Email: hammer@umn.edu 
Phone: 612-624-5641  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Minnesota 
Comments:  
Co-Investigator(s) / Affiliation:  Dutton, James  Ph.D./ University of Minnesota  Kidder, Louis  Ph.D./ University of Minnesota 
Project Information: Grant/Contract No. NNX15AB38G 
Responsible Center: NASA ARC 
Grant Monitor: Smith, Jeffrey  
Center Contact: 650-604-0880 
jeffrey.d.smith2@nasa.gov 
Solicitation: 2014 Space Biology Flight NNH14ZTT001N 
Grant/Contract No.: NNX15AB38G 
Project Type: FLIGHT  
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Cell & Molecular Biology
Space Biology Cross-Element Discipline: (1) Developmental Biology
Space Biology Special Category: (1) Cell Culture
Task Description: We propose to investigate the effect of gravity on fundamental properties of mammalian stem cells during differentiation of 3-D cultures of induced pluripotent stem (iPS) cells. Experiments aboard the ISS, STS, and ground-based simulations have demonstrated that microgravity influences gene expression, cell proliferation, and differentiation in stem cells. However, the mechanism behind these observations is not clearly understood. In this study we will investigate how exposure to microgravity fundamentally alters the regulation of Oct4, a transcription factor necessary to maintain pluripotency, and how these changes can affect the timing, progression, and outcomes of cell differentiation. Our laboratory has created an Oct4:CreER mTmG transgenic mouse that, for the first time, allows lineage tracing of Oct4 expression in stem cells and their progeny. We will use iPS cells derived from this model to determine the influence of microgravity on the loss of pluripotency and differentiation.

During the Flight Definition Phase we will use magnetic levitation, a unique ground-based simulation of orbital free fall, to optimize execution of the Spaceflight Experiment Phase. This approach will maximize the success of space-based studies. We propose to investigate the effect of gravity on the timing and spatial arrangement of the loss of Oct4 expression in differentiating iPS cell aggregates. We will also examine the effect of gravity on gene expression in cohorts of Oct4 expressing and non-expressing cells during differentiation by comparing the results of ground-based experiments to those conducted on orbit. Finally, we will explore mechanisms behind the effect of microgravity on both Oct4 gene regulation and control of downstream gene expression by Oct4. This work will determine the effect of spaceflight on changes in Oct4 gene expression during differentiation of pluripotent stem cells and the consequences of these changes on differentiation outcomes. This will increase our understanding of fundamental stem cell behavior in microgravity.

 

Research Impact/Earth Benefits: 0

 

Task Progress & Bibliography Information FY2015 
Task Progress: New project for FY2015.

 

Bibliography Type: Description: (Last Updated: )  Show Cumulative Bibliography Listing
 
 None in FY 2015