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In Vivo Direct Reprogramming of Resident Glial Cells into Interneurons by Intracerebral Injection of Viral Vectors
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Enhanced efficiency of nonviral direct neuronal reprogramming on topographical patterns
Sabrina Mattiassi1, Muhammad Rizwan, Christopher L Grigsby
1Department of Chemical Engineering, University of Waterloo, 200 University Ave. W, Waterloo, Ontario N2L 3G1, Canada. eyim@uwaterloo.ca.
Biomaterials Science
|June 15, 2021
Summary
Topographical cues significantly boost nonviral direct neuronal reprogramming efficiency. This method enhances fibroblast conversion into induced neurons, offering a promising advancement for regenerative medicine applications.
Area of Science:
- Biotechnology
- Regenerative Medicine
- Neuroscience
Background:
- Nonviral direct neuronal reprogramming is crucial for tissue engineering but limited by low efficiency.
- Topographical cues have previously enhanced stem cell differentiation and transdifferentiation.
Purpose of the Study:
- To investigate if topographical cues can improve nonviral direct neuronal reprogramming efficiency.
- To identify specific patterns that enhance fibroblast-to-neuron conversion.
Main Methods:
- Used a polymer-BAM factor transfection polyplex to reprogram mouse embryonic fibroblasts.
- Screened various patterns on a multi-architecture chip for optimal reprogramming.
- Analyzed protein expression (TUJ1, MAP2), cell morphology, and electrophysiological function.
Main Results:
- Hierarchical topographies (nanopatterns on micropatterns) significantly increased TUJ1+ and MAP2+ cells.
- Microscale patterns enhanced initial factor expression, while nanoscale patterns promoted neuronal maturation.
- Nanoscale patterns yielded induced neurons with action potential firing and spontaneous synaptic activity.
Conclusions:
- Topographical cues, particularly hierarchical patterns, substantially enhance nonviral direct neuronal reprogramming.
- This approach improves efficiency, making it comparable to higher doses of reprogramming factors without topography.
- Topography offers a promising strategy to advance regenerative medicine and neural tissue engineering.
