hiPSC Disease Modeling of Rare Hereditary Cerebellar Ataxias: Opportunities and Future Challenges

Autores de CIPF

• Dunja Lukovic

  Autor

• 

  M Victoria Moreno Manzano

  Autor

• 

  Francisco Rodríguez Jiménez

  Autor

• 

  Slaven Erceg Vukicevic

  Autor

Participantes ajenos a CIPF

• Vilches, A
• Sykova, E
• Jendelova, P
• Stojkovic, M

Grupos de Investigación

• Laboratorio de Regeneración Tisular y Neuronal

  

  Jefe/a de Grupo

  M Victoria Moreno Manzano

• Laboratorio Terapias con Células Madre en Enfermedades Neurodegenerativas

  

  Jefe/a de Grupo

  Slaven Erceg Vukicevic

Abstract

Cerebellar ataxias are clinically and genetically heterogeneous diseases affecting primary cerebellar cells. The lack of availability of affected tissue from cerebellar ataxias patients is the main obstacle in investigating the pathogenicity of these diseases. The landmark discovery of human-induced pluripotent stem cells (hiPSC) has permitted the derivation of patient-specific cells with an unlimited self-renewing capacity. Additionally, their potential to differentiate into virtually any cell type of the human organism allows for large amounts of affected cells to be generated in culture, converting this hiPSC technology into a revolutionary tool in the study of the mechanisms of disease, drug discovery, and gene correction. In this review, we will summarize the current studies in which hiPSC were utilized to study cerebellar ataxias. Describing the currently available 2D and 3D hiPSC-based cellular models, and due to the fact that extracerebellar cells were used to model these diseases, we will discuss whether or not they represent a faithful cellular model and whether they have contributed to a better understanding of disease mechanisms.

Keywords

• induced pluripotent stem cells; disease modelling; ataxia; 3D organoids