Advances and challenges in modeling inherited peripheral neuropathies using iPSCs

Area of Science:

• Neuroscience
• Genetics
• Cell Biology

Background:

• Inherited peripheral neuropathies (IPNs) are genetic disorders affecting peripheral nerve development and function.
• Advances in molecular mechanisms and animal models have not yet yielded clinical treatments for IPNs.
• There is a critical need for more relevant human models to study IPNs and develop therapies.

Purpose of the Study:

• To review current in vitro human cellular models for inherited peripheral neuropathies.
• To highlight the potential of patient-specific induced pluripotent stem cells (iPSCs) for IPN modeling.
• To discuss recent advancements in complex iPSC-based IPN models.

Main Methods:

• Review of existing literature on in vitro IPN models.
• Focus on induced pluripotent stem cell (iPSC) derivatives in 2D monocultures.
• Exploration of advanced iPSC-based systems including microfluidic chips, organoids, and assembloids.

Main Results:

• Significant progress in understanding IPN molecular mechanisms through cellular and animal models.
• Patient-specific iPSCs offer a powerful platform for disease modeling and preclinical studies.
• Emerging complex iPSC models (microfluidics, organoids, assembloids) provide greater biological relevance.

Conclusions:

• Despite advances, no clinical treatments for IPNs are currently available.
• Patient-derived iPSC models are crucial for advancing IPN research and therapeutic development.
• Complex iPSC-based systems represent the next frontier in creating biologically relevant IPN models for preclinical testing.