Human stem cell models of neurodegeneration: From basic science of amyotrophic lateral sclerosis to clinical translation

Elisa Giacomelli; Björn F Vahsen; Elizabeth L Calder; Yinyan Xu; Jakub Scaber; Elizabeth Gray; Ruxandra Dafinca; Kevin Talbot; Lorenz Studer

doi:10.1016/j.stem.2021.12.008

Human stem cell models of neurodegeneration: From basic science of amyotrophic lateral sclerosis to clinical translation

Cell Stem Cell. 2022 Jan 6;29(1):11-35. doi: 10.1016/j.stem.2021.12.008.

Authors

Elisa Giacomelli¹, Björn F Vahsen², Elizabeth L Calder¹, Yinyan Xu³, Jakub Scaber², Elizabeth Gray², Ruxandra Dafinca², Kevin Talbot⁴, Lorenz Studer⁵

Affiliations

¹ The Center for Stem Cell Biology, Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA.
² Oxford Motor Neuron Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
³ Oxford Motor Neuron Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; Chinese Academy of Medical Sciences (CAMS), CAMS Oxford Institute (COI), Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
⁴ Oxford Motor Neuron Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address: [email protected].
⁵ The Center for Stem Cell Biology, Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA. Electronic address: [email protected].

Abstract

Neurodegenerative diseases are characterized by progressive cell loss leading to disruption of the structure and function of the central nervous system. Amyotrophic lateral sclerosis (ALS) was among the first of these disorders modeled in patient-specific iPSCs, and recent findings have translated into some of the earliest iPSC-inspired clinical trials. Focusing on ALS as an example, we evaluate the status of modeling neurodegenerative diseases using iPSCs, including methods for deriving and using disease-relevant neuronal and glial lineages. We further highlight the remaining challenges in exploiting the full potential of iPSC technology for understanding and potentially treating neurodegenerative diseases such as ALS.

Keywords: ALS; FTD; astrocytes; clinical translation; disease modeling; microglia; motor neurons: cortical neurons; neurodegenerative diseases; pluripotent stem cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Amyotrophic Lateral Sclerosis* / therapy
Humans
Induced Pluripotent Stem Cells*
Neuroglia
Neurons

Abstract

Publication types

MeSH terms

Grants and funding