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

  • Kenyi Saito-Diaz
  • Nadja Zeltner
Review article

Abstract

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.

Keywords

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 

Abbreviations

PNS

Peripheral nervous system

ANS

Autonomic nervous system

CNS

Central nervous system

ENS

Enteric nervous system

iPSCs

Induced pluripotent stem cells

hPSCs

Human pluripotent stem cells

hiPSCs

Human induced pluripotent stem cells

hESCs

Human embryonic stem cells

FD

Familial dysautonomia

HD

Hirschsprung’s disease

NCCs

Neural crest cells

SAP

Sympathoadrenal progenitor

hOR-MSCs

Human olfactory ecto-mesenchymal stem cells

HIOs

Intestinal human organoids

GI

Gastrointestinal tract

Notes

Acknowledgements

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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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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