Enabling non-genetic activity-driven maturation of iPSC-derived neurons
Grant Award Details
Grant Type:
Grant Number:
DISC2-13483
Investigator(s):
Human Stem Cell Use:
Award Value:
$675,000
Status:
Active
Progress Reports
Reporting Period:
NCE Year 2
Grant Application Details
Application Title:
Enabling non-genetic activity-driven maturation of iPSC-derived neurons
Public Abstract:
Research Objective
We will empower stem cell biologists to generate iPSC-derived neurons faster and with enhanced maturation by enabling optical cell stimulation and triggering activity-dependent maturation processes
Impact
Our project will address such critical bottlenecks as insufficient maturity of iPSC-derived neurons that limits their utility in age-related neurological disorders that manifest later in life.
Major Proposed Activities
We will empower stem cell biologists to generate iPSC-derived neurons faster and with enhanced maturation by enabling optical cell stimulation and triggering activity-dependent maturation processes
Impact
Our project will address such critical bottlenecks as insufficient maturity of iPSC-derived neurons that limits their utility in age-related neurological disorders that manifest later in life.
Major Proposed Activities
- To fabricate graphene-based substrates for iPSC-derived neurons and human brain cortical organoids in order to use them during subsequent activities for optical cell stimulation
- To subject iPSC-derived neurons to repeated patterns of optical stimulation over extended periods of time in order to trigger the electrical activity in neuronal networks
- To characterize the changes in functional activity of optically stimulated iPSC-derived neurons that occurred as a result of different optical stimulation protocols
- To characterize the impact of the cell activity triggered by optical stimulation on transcriptional and cell population dynamics during activity-dependent maturation
- To finalize the validated protocols for light-driven activity-dependent enhanced maturation of iPSC-derived neurons.
Statement of Benefit to California:
Neurological disorders are the leading cause of disability and the second leading cause of death. Disease models based on iPSC-neurons allow us to better understand the disease mechanisms and to develop efficacious treatments. However, these neurons often do not exhibit adult-like maturation, limiting the clinical predictiveness of adult disease models. We propose to address this bottleneck by enabling activity-dependent maturation via long-term graphene-based optical stimulation of neurons.
Publications
- Front Bioeng Biotechnol (2023): Graphene-based cardiac sensors and actuators. (PubMed: 37256116)
