Modeling of skeletal development and diseases using human pluripotent stem cells

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Regenerative Medicine

Background:

• Human skeletal elements originate from diverse embryonic sources, including neural crest, paraxial mesoderm, and lateral plate mesoderm.
• Skeletal development is a complex process orchestrated by coordinated signaling pathways during distinct embryonic stages.

Purpose of the Study:

• To review current understanding of embryonic skeletal development.
• To introduce state-of-the-art human pluripotent stem cell (hPSC) methods for modeling skeletal development, metabolism, and diseases.
• To discuss limitations and future perspectives of hPSC-based skeletal modeling in precision medicine.

Main Methods:

• Utilizing human pluripotent stem cells (hPSCs) to model skeletal development.
• Employing stepwise protocols to generate skeletal cells mimicking developmental pathways.
• Applying organoid methods for multicellular organization and recapitulation of skeletal development and metabolism.
• Modeling genetic skeletal diseases using patient-derived induced pluripotent stem cells and genome editing.

Main Results:

• Established hPSC-based models effectively recapitulate key aspects of skeletal development.
• Organoid systems allow for the study of complex multicellular skeletal organization and metabolism.
• Patient-derived iPSC models coupled with genome editing enable the study of skeletal diseases.
• Model-based drug screening platforms are emerging as powerful tools for therapeutic development.

Conclusions:

• hPSC-based modeling systems offer significant potential for advancing the understanding and treatment of skeletal disorders.
• Future applications in precision medicine are anticipated, leveraging these advanced modeling techniques.
• Continued research is crucial to overcome current limitations and fully realize the potential of hPSC-based skeletal modeling.