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Organotypic Collagen I Assay: A Malleable Platform to Assess Cell Behaviour in a 3-Dimensional Context
Published on: October 13, 2011
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Local FK506 dose-dependent study using a novel three-dimensional organotypic assay
Kasra Tajdaran1,2, Katelyn Chan1,2, Jennifer Zhang1,3,4
1Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
Biotechnology and Bioengineering
|October 23, 2018
Summary
Local administration of FK506 (a neuroregenerative drug) shows promise for peripheral nerve repair. Optimal doses of 1 pg/ml and 100 ng/ml were identified, with targeted delivery to growing axons enhancing regeneration.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Drug Delivery Systems
Background:
- Systemic FK506 (immunosuppressant) has neuroregenerative potential but causes side effects.
- Local FK506 delivery is promising for peripheral nerve regeneration, yet optimal dosing remains undetermined.
Purpose of the Study:
- To establish the optimal local dose of FK506 for enhancing peripheral nerve axon regeneration.
- To investigate the effect of targeted FK506 delivery to neurites versus systemic delivery.
Main Methods:
- Developed a 3D organotypic assay using dorsal root ganglion (DRG) and acellular nerve allograft (ANA) to mimic peripheral nerves.
- Adapted a 3D compartmented system for localized FK506 delivery to growing neurites in vitro.
- Evaluated neurite extension and density across various FK506 concentrations.
Main Results:
- A bimodal dose response was observed, with peak neurite extension at 1 pg/ml and 100 ng/ml FK506.
- Targeted delivery of FK506 to growing neurites significantly increased neurite extension and density.
- Delivery to both neurites and neural cell bodies did not yield the same regenerative enhancement.
Conclusions:
- Identified optimal local FK506 concentrations for peripheral nerve regeneration.
- Demonstrated that localized drug delivery to axons, not cell bodies, is crucial for enhanced regeneration.
- Suggests FK506 may interact directly with axons at the growth cone level.
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