Translational Capabilities: Improved iPSC protocols (Milestone 4.F)
In Progress
Timeline Start - End
2016 - 2024Research Implementation Area
Translational Tools, Infrastructure, and CapabilitiesDevelop improved iPSC protocols for all relevant cell types and human-based organoid model systems.
Support the development of co-culture systems utilizing 3D organoid-like spheres to recapitulate complex interactions in a dish and develop novel ex-vivo models of “cognition in a dish” and “ancestry in a dish” for precision medicine research.
Invest in the development of high-throughput systems of AD-relevant cells and organoids driven by robotics with digital read-outs (such as high content imaging) to leverage reinforcement learning techniques for more data-driven target discovery/screening.
Success Criteria
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Establish infrastructure to develop standardized and deeply phenotyped in vitro model resources, including iPSC-based and primary cells, brain slice and organoid models.
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Establish the translational validity of these in vitro models to recapitulate the molecular/network perturbations identified in the individual (human or animal) from which the in vitro model was generated.
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Ensure rapid and broad distribution of the cell-based and organoid research models, data, and analytical methods for use in basic research and therapy development, similar to the open-science/open source principles of the MODEL-AD Consortium.
Summary of Key Accomplishments
NIA supports the development of iPSC and 3D organoids (small, 3D tissue cultures that are derived from stem cells and that can replicate the complexity of an organ) as tools for basic and translational research through two targeted funding initiatives associated with the AD Research Centers Network as well as via investigator-initiated research. The AD Research Center at UC Irvine has established a National Alzheimer’s Disease iPS Cell Bank aimed at developing and sharing these research tools with the research community to better understand the biology of AD and develop therapies. Also, the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD) is biobanking iPS cells and fibroblast lines and making these research tools available to the research community.
The key accomplishments summary is current as of March 2022.
Accomplishments/Implementation Activities
Funding Initiatives
- RFA-AG-14-012: Human Cell Reprogramming for Functional Genetics of Alzheimer’s Disease (R01)
- RFA-AG-17-009: Impact of Aging in Human Cell Models of Alzheimer’s Disease (R01)
- PAR-18-516: Human Cell Biology of Alzheimer's Disease Genetic Variants (R01)
- RFA-AG-19-010: Alzheimer Centers for Discovery of New Medicines (U54)
- NOT-AG-21-052: Human Cell Biology of Alzheimer's Disease Genetic Variants (reissue of PAR-18-516)
Research Programs and Resources
- UC Irvine ADRC iPSC Core
- iPSCs and Fibroblast lines at NCRAD
- UCSD ADRC iPSC Core
- Examples of Funded Projects
- Treat AD Centers