From mice to clinical relevance: humanizing neuroscience with human-based model systems.

Area of Science:

• Neuroscience
• Translational Research
• Biomedical Engineering

Background:

• Traditional animal models in neuroscience research have limitations in human disease translation.
• Interspecific differences between animal models and humans frequently lead to clinical trial failures.
• The unique complexity of the human brain necessitates alternative research models.

Purpose of the Study:

• To critically evaluate the advantages and disadvantages of animal models in neuroscience.
• To review the development and current applications of human-based research models.
• To explore the potential of human-based systems to complement or replace animal models and reduce the translational gap.

Main Methods:

• Review of existing literature on animal models and human-based neuroscience research systems.
• Critical discussion of various human-based models: dissociated neuronal cultures, stem cell-derived platforms (organoids), micro-engineered devices, and human brain slices.
• Analysis of challenges including human variability, technical hurdles, ethical considerations, and regulatory issues.

Main Results:

• Animal models provide mechanistic insights but suffer from poor translational power.
• Human-based models (organoids, brain slices, etc.) offer improved recapitulation of human physiology and pathology.
• These novel systems present distinct benefits and limitations for studying neural circuits, diseases, and therapeutic responses.

Conclusions:

• Human-based models represent a significant advancement for more predictive and ethically responsible neuroscientific research.
• These models have the potential to significantly decrease the translational gap between preclinical findings and clinical applications.
• Addressing challenges in human variability, technology, ethics, and regulation is crucial for the advancement of human brain research.