Opportunities and challenges of pluripotent stem cell neurodegenerative disease models

  title={Opportunities and challenges of pluripotent stem cell neurodegenerative disease models},
  author={Jackson Sandoe and Kevin C Eggan},
  journal={Nature Neuroscience},
Human neurodegenerative disorders are among the most difficult to study. In particular, the inability to readily obtain the faulty cell types most relevant to these diseases has impeded progress for decades. Recent advances in pluripotent stem cell technology now grant access to substantial quantities of disease-pertinent neurons both with and without predisposing mutations. While this suite of technologies has revolutionized the field of 'in vitro disease modeling', great care must be taken in… 

Toward stem cell-based phenotypic screens for neurodegenerative diseases

It is illustrated how analysis in the simple baker's yeast cell Saccharaomyces cerevisiae is driving discovery in patient-derived neurons, and how approaches in this model organism can establish a paradigm to guide the development of stem cell-based phenotypic screens.

Induced pluripotent stem cells and neurological disease models.

This review focuses on the prospective applications of different stem cell types for disease modeling and drug screening and how the availability of patient-specific induced pluripotent stem cells (iPS cells) offers a unique opportunity for studying and modeling human neurodevelopmental and neurodegenerative diseases in vitro and for testing small molecules or other potential therapies for these disorders.

Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development

An overview of human stem cell models of neurodegeneration using iPS cells from patients with Alzheimer's disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington’S disease, spinal muscular atrophy and other Neurodegenerative diseases is provided.

Stem Cells on the Brain: Modeling Neurodevelopmental and Neurodegenerative Diseases Using Human Induced Pluripotent Stem Cells

Progress in the field of induced pluripotent stem cells is reviewed and both the advantages and potential pitfalls of modeling neurodegenerative and neurodevelopmental diseases using this technology are described.

Probing disorders of the nervous system using reprogramming approaches

Tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported are presented, the current state of the field is described, important breakthroughs are highlighted and the next steps and future challenges are discussed.

Probing disorders of the nervous system

Tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported are presented, the current state of the field is described, important breakthroughs are highlighted and the next steps and future challenges are discussed.

Reprogramming patient-derived cells to study the epilepsies

The progress made and the distinct advantages and limitations of using patient-derived cells to study or treat epilepsy are discussed, as well as critical future directions for the field.

Modeling genetic epilepsies in a dish

  • W. NiuJ. Parent
  • Biology
    Developmental dynamics : an official publication of the American Association of Anatomists
  • 2019
Previous work using both 2D and 3D hPSC models of genetic epilepsies, as well as recent advances in the field are reviewed.

A practical guide to induced pluripotent stem cell research using patient samples

The areas where patient iPSC studies have provided truly valuable information beyond existing skepticism are summarized, the desired technologies to overcome current limitations are discussed and practical guidance for how to utilize the resources are included.

Advances in reprogramming-based study of neurologic disorders.

Limits of currently available reprogramming-based methods in faithfully and reproducibly recapitulating disease pathology are discussed and issues such as culture heterogeneity, interline and inter-individual variability, and limitations of two-dimensional differentiation paradigms are addressed.



Induced pluripotent stem cells: the new patient?

Worldwide increases in life expectancy have been paralleled by a greater prevalence of chronic and age-associated disorders, particularly of the cardiovascular, neural and metabolic systems. This has

Progress toward the clinical application of patient-specific pluripotent stem cells.

The current state of iPS cell technology is described, including approaches by which they are generated and what is known about their biology, and the potential applications of these cells for disease modeling, drug discovery, and, eventually, cell replacement therapy are discussed.

Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons

Induced pluripotent stem cells are generated from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.

Induced pluripotent stem cells from a spinal muscular atrophy patient

This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease and represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.

Neuronal Properties, In Vivo Effects, and Pathology of a Huntington's Disease Patient‐Derived Induced Pluripotent Stem Cells

Results indicate that, although HD‐iPSC carrying 72 CAG repeats can form GABAergic neurons and give rise to functional effects in vivo, without showing an overt HD phenotype, it is highly susceptible to proteasome inhibition and develops HD pathology at later stages of transplantation.