BDNF Overexpression Enhances Neuronal Activity and Axonal Growth in Human iPSC-Derived Neural Cultures

Area of Science:

• Neuroscience
• Stem Cell Biology
• Regenerative Medicine

Background:

• Aging populations face rising neurodegenerative diseases and neural injuries.
• The brain's limited regeneration necessitates strategies for neuronal repair.
• Brain-derived neurotrophic factor (BDNF) is crucial for neuronal development and plasticity.

Purpose of the Study:

• To investigate if constitutive BDNF expression in human iPSC-derived NPCs enhances neurogenesis and integration in vitro.
• To assess the impact of sustained BDNF on neuronal maturation, activity, and network formation.

Main Methods:

• Engineering human induced pluripotent stem cell-derived neural progenitor cells (iPSCs-NPCs) for constitutive BDNF overexpression.
• Culturing engineered NPCs to form neuronal networks in vitro.
• Utilizing compartmentalized microfluidic systems to analyze axonal outgrowth and directed extension.

Main Results:

• BDNF-overexpressing NPCs yielded neuronal cultures with increased mature, spontaneously active neurons.
• Axonal outgrowth was significantly enhanced, with directed extension observed in microfluidic systems, indicating chemoattraction.
• Network structure and organization remained unaltered, and effects mimicked early recombinant BDNF supplementation.

Conclusions:

• Sustained BDNF expression in iPSC-derived NPCs promotes neuronal maturation and axonal projection.
• This strategy accelerates functional neural network development in vitro without compromising network integrity.
• BDNF can serve as a therapeutic agent and a tool to enhance cell therapy and in vitro neural network development.