iPSC modeling of rare pediatric disorders

Bethany A. Freel, Jordan N. Sheets, Kevin R. Francis

Research output: Contribution to journalReview article

Abstract

Discerning the underlying pathological mechanisms and the identification of therapeutic strategies to treat individuals affected with rare neurological diseases has proven challenging due to a host of factors. For instance, rare diseases affecting the nervous system are inherently lacking in appropriate patient sample availability compared to more common diseases, while animal models often do not accurately recapitulate specific disease phenotypes. These challenges impede research that may otherwise illuminate aspects of disease initiation and progression, leading to the ultimate identification of potential therapeutics. The establishment of induced pluripotent stem cells (iPSCs) as a human cellular model with defined genetics has provided the unique opportunity to study rare diseases within a controlled environment. iPSC models enable researchers to define mutational effects on specific cell types and signaling pathways within increasingly complex systems. Among rare diseases, pediatric diseases affecting neurodevelopment and neurological function highlight the critical need for iPSC-based disease modeling due to the inherent difficulty associated with collecting human neural tissue and the complexity of the mammalian nervous system. Rare neurodevelopmental disorders are therefore ideal candidates for utilization of iPSC-based in vitro studies. In this review, we address both the state of the iPSC field in the context of their utility and limitations for neurodevelopmental studies, as well as speculating about the future applications and unmet uses for iPSCs in rare diseases.

Original languageEnglish (US)
Article number108533
JournalJournal of Neuroscience Methods
Volume332
DOIs
StatePublished - Feb 15 2020

Fingerprint

Induced Pluripotent Stem Cells
Rare Diseases
Pediatrics
Nervous System
Animal Disease Models
Controlled Environment
Disease Progression
Research Personnel
Phenotype
Therapeutics
Research

Keywords

  • Disease modeling
  • Embryonic
  • Induced pluripotent stem cell
  • Neural differentiation
  • Neurodevelopment
  • Neuronal differentiation
  • Pluripotency
  • Rare disease
  • Reprogramming
  • Stem cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

iPSC modeling of rare pediatric disorders. / Freel, Bethany A.; Sheets, Jordan N.; Francis, Kevin R.

In: Journal of Neuroscience Methods, Vol. 332, 108533, 15.02.2020.

Research output: Contribution to journalReview article

Freel, Bethany A. ; Sheets, Jordan N. ; Francis, Kevin R. / iPSC modeling of rare pediatric disorders. In: Journal of Neuroscience Methods. 2020 ; Vol. 332.
@article{c2227d6519ae42af9f231600c1b03018,
title = "iPSC modeling of rare pediatric disorders",
abstract = "Discerning the underlying pathological mechanisms and the identification of therapeutic strategies to treat individuals affected with rare neurological diseases has proven challenging due to a host of factors. For instance, rare diseases affecting the nervous system are inherently lacking in appropriate patient sample availability compared to more common diseases, while animal models often do not accurately recapitulate specific disease phenotypes. These challenges impede research that may otherwise illuminate aspects of disease initiation and progression, leading to the ultimate identification of potential therapeutics. The establishment of induced pluripotent stem cells (iPSCs) as a human cellular model with defined genetics has provided the unique opportunity to study rare diseases within a controlled environment. iPSC models enable researchers to define mutational effects on specific cell types and signaling pathways within increasingly complex systems. Among rare diseases, pediatric diseases affecting neurodevelopment and neurological function highlight the critical need for iPSC-based disease modeling due to the inherent difficulty associated with collecting human neural tissue and the complexity of the mammalian nervous system. Rare neurodevelopmental disorders are therefore ideal candidates for utilization of iPSC-based in vitro studies. In this review, we address both the state of the iPSC field in the context of their utility and limitations for neurodevelopmental studies, as well as speculating about the future applications and unmet uses for iPSCs in rare diseases.",
keywords = "Disease modeling, Embryonic, Induced pluripotent stem cell, Neural differentiation, Neurodevelopment, Neuronal differentiation, Pluripotency, Rare disease, Reprogramming, Stem cell",
author = "Freel, {Bethany A.} and Sheets, {Jordan N.} and Francis, {Kevin R.}",
year = "2020",
month = "2",
day = "15",
doi = "10.1016/j.jneumeth.2019.108533",
language = "English (US)",
volume = "332",
journal = "Journal of Neuroscience Methods",
issn = "0165-0270",
publisher = "Elsevier",

}

TY - JOUR

T1 - iPSC modeling of rare pediatric disorders

AU - Freel, Bethany A.

AU - Sheets, Jordan N.

AU - Francis, Kevin R.

PY - 2020/2/15

Y1 - 2020/2/15

N2 - Discerning the underlying pathological mechanisms and the identification of therapeutic strategies to treat individuals affected with rare neurological diseases has proven challenging due to a host of factors. For instance, rare diseases affecting the nervous system are inherently lacking in appropriate patient sample availability compared to more common diseases, while animal models often do not accurately recapitulate specific disease phenotypes. These challenges impede research that may otherwise illuminate aspects of disease initiation and progression, leading to the ultimate identification of potential therapeutics. The establishment of induced pluripotent stem cells (iPSCs) as a human cellular model with defined genetics has provided the unique opportunity to study rare diseases within a controlled environment. iPSC models enable researchers to define mutational effects on specific cell types and signaling pathways within increasingly complex systems. Among rare diseases, pediatric diseases affecting neurodevelopment and neurological function highlight the critical need for iPSC-based disease modeling due to the inherent difficulty associated with collecting human neural tissue and the complexity of the mammalian nervous system. Rare neurodevelopmental disorders are therefore ideal candidates for utilization of iPSC-based in vitro studies. In this review, we address both the state of the iPSC field in the context of their utility and limitations for neurodevelopmental studies, as well as speculating about the future applications and unmet uses for iPSCs in rare diseases.

AB - Discerning the underlying pathological mechanisms and the identification of therapeutic strategies to treat individuals affected with rare neurological diseases has proven challenging due to a host of factors. For instance, rare diseases affecting the nervous system are inherently lacking in appropriate patient sample availability compared to more common diseases, while animal models often do not accurately recapitulate specific disease phenotypes. These challenges impede research that may otherwise illuminate aspects of disease initiation and progression, leading to the ultimate identification of potential therapeutics. The establishment of induced pluripotent stem cells (iPSCs) as a human cellular model with defined genetics has provided the unique opportunity to study rare diseases within a controlled environment. iPSC models enable researchers to define mutational effects on specific cell types and signaling pathways within increasingly complex systems. Among rare diseases, pediatric diseases affecting neurodevelopment and neurological function highlight the critical need for iPSC-based disease modeling due to the inherent difficulty associated with collecting human neural tissue and the complexity of the mammalian nervous system. Rare neurodevelopmental disorders are therefore ideal candidates for utilization of iPSC-based in vitro studies. In this review, we address both the state of the iPSC field in the context of their utility and limitations for neurodevelopmental studies, as well as speculating about the future applications and unmet uses for iPSCs in rare diseases.

KW - Disease modeling

KW - Embryonic

KW - Induced pluripotent stem cell

KW - Neural differentiation

KW - Neurodevelopment

KW - Neuronal differentiation

KW - Pluripotency

KW - Rare disease

KW - Reprogramming

KW - Stem cell

UR - http://www.scopus.com/inward/record.url?scp=85076136198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076136198&partnerID=8YFLogxK

U2 - 10.1016/j.jneumeth.2019.108533

DO - 10.1016/j.jneumeth.2019.108533

M3 - Review article

C2 - 31811832

AN - SCOPUS:85076136198

VL - 332

JO - Journal of Neuroscience Methods

JF - Journal of Neuroscience Methods

SN - 0165-0270

M1 - 108533

ER -