Induced pluripotent stem cells for disease modeling, cell therapy and drug discovery in genetic autonomic disorders: a review

  • Kenyi Saito-Diaz
  • Nadja ZeltnerEmail author
Review article


The autonomic nervous system (ANS) regulates all organs in the body independent of consciousness, and is thus essential for maintaining homeostasis of the entire organism. Diseases of the ANS can arise due to environmental insults such as injury, toxins/drugs and infections or due to genetic lesions. Human studies and animal models have been instrumental to understanding connectivity and regulation of the ANS and its disorders. However, research into cellular pathologies and molecular mechanisms of ANS disorders has been hampered by the difficulties in accessing human patient-derived ANS cells in large numbers to conduct meaningful research, mainly because patient neurons cannot be easily biopsied and primary human neuronal cultures cannot be expanded.

Human-induced pluripotent stem cell (hiPSC) technology can elegantly bridge these issues, allowing unlimited access of patient-derived ANS cell types for cellular, molecular and biochemical analysis, facilitating the discovery of novel therapeutic targets, and eventually leading to drug discovery. Additionally, such cells may provide a source for cell replacement therapy to replenish lost or injured ANS tissue in patients.

Here, we first review the anatomy and embryonic development of the ANS, as this knowledge is crucial for understanding disease modeling approaches. We then review the current advances in human stem cell technology for modeling diseases of the ANS, recent strides toward cell replacement therapy and drug discovery initiatives.


ANS disease Human pluripotent stem cells Induced pluripotent stem cells Embryonic stem cells Disease modeling Disease mechanism Cell therapy Drug discovery Familial dysautonomia Hirschsprung’s disease Neural crest Stem cells In vitro differentiation 



Peripheral nervous system


Autonomic nervous system


Central nervous system


Enteric nervous system


Induced pluripotent stem cells


Human pluripotent stem cells


Human induced pluripotent stem cells


Human embryonic stem cells


Familial dysautonomia


Hirschsprung’s disease


Neural crest cells


Sympathoadrenal progenitor


Human olfactory ecto-mesenchymal stem cells


Intestinal human organoids


Gastrointestinal tract



We would like to thank Issa P. Bagayogo and Oliver Harschnitz for critical reading of our manuscript.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center for Molecular MedicineUniversity of GeorgiaAthensUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of GeorgiaAthensUSA
  3. 3.Department of Cellular BiologyUniversity of GeorgiaAthensUSA

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