Photo: (left to right) "Neural spheres at Day 1, Day 4 and Day 8 cultured in the grooves of the micropatterned surface"
An interdisciplinary research effort at the Centre for Molecular Medicine and Biobanking, University of Malta that combines stem cell therapy, neuronal biology, and microfabrication in an effort to solve the issue of culturing stem cells, differentiating them into neurons, and testing neuronal properties has just come to the end of its first phase.
A major obstacle to the investigation of in vitro neuronal properties and the assessment of neuromodulatory compounds, such as potential treatments for neurodegenerative diseases like Parkinson's or Alzheimer's, is the current difficulty in obtaining optimised surfaces for stem cell differentiation into nerve cell lineages.
The MicroFab-Neuro team led by Dr Byron Baron set out to develop a micro-patterned surface using microfabrication technology with grooves about the diameter of a cell to aid researchers culture organised patterns of stem cells, promote their differentiation into neurons mimicking natural synapses, and then test the derived neurons on a single surface, ensuring their therapeutic potential. This would shorten testing times and reduce costs by eliminating the need for cell culture components and handling between procedures.
Published literature shows that when cells are in culture, they align themselves with grooves etched into the culturing surface and move along them in response to their width and depth. This project combines microfluidic principles with 2D fabrication techniques on biocompatible polymer surfaces to strike a balance between organised 3D microfluidic channels that are expensive, laborious and offer very limited access for testing, and easy but disorganised cell culturing obtained in conventional 2D culture systems.
Stem cell cultures from umbilical cord are being differentiated into dopaminergic neurones and having their protein markers analysed on the test surfaces generated. This offers a more streamlined and simplified process for culturing and testing stem cells while maintaining the biological relevance of neuronal cells for therapeutic applications.
Ultimately, this would be an invaluable tool for both basic research and drug discovery as it would provide a platform to examine the intricate behaviours of cells, as well as testing potential treatments in a much more controlled environment than previously possible. This technology has the added benefit of reducing the dependence on and need for animal models by enabling the organised culture of neuronal cells derived from stem cells in a more dispersed, natural conformation, well suited for R&D applications.
Additionally, it would impact society at large by increasing the availability of patient-specific cell therapies, such as stem cells for nerve and tissue damage repair, with the highest probability of success.
