Spinal Cord Organoids to Study Motor Neuron Development and Disease

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

Abstract

Motor neuron diseases (MNDs) are a heterogeneous group of disorders that affect the cranial and/or spinal motor neurons (spMNs), spinal sensory neurons and the muscular system. Although they have been investigated for decades, we still lack a comprehensive understanding of the underlying molecular mechanisms; and therefore, efficacious therapies are scarce. Model organisms and relatively simple two-dimensional cell culture systems have been instrumental in our current knowledge of neuromuscular disease pathology; however, in the recent years, human 3D in vitro models have transformed the disease-modeling landscape. While cerebral organoids have been pursued the most, interest in spinal cord organoids (SCOs) is now also increasing. Pluripotent stem cell (PSC)-based protocols to generate SpC-like structures, sometimes including the adjacent mesoderm and derived skeletal muscle, are constantly being refined and applied to study early human neuromuscular development and disease. In this review, we outline the evolution of human PSC-derived models for generating spMN and recapitulating SpC development. We also discuss how these models have been applied to exploring the basis of human neurodevelopmental and neurodegenerative diseases. Finally, we provide an overview of the main challenges to overcome in order to generate more physiologically relevant human SpC models and propose some exciting new perspectives.

Details

Original languageEnglish
Article number1254
Journal Life : open access journal
Volume13
Issue number6
Publication statusPublished - 25 May 2023
Peer-reviewedYes

External IDs

PubMed 37374039
WOS 001017263300001
Scopus 85163770134
Mendeley 6b709839-155a-3d25-be2a-0ace300a4ba1

Keywords

Research priority areas of TU Dresden

DFG Classification of Subject Areas according to Review Boards

Sustainable Development Goals

Keywords

  • Development, In vitro disease modeling, Organoids, induced pluripotent stem cells (iPSCs), motor neuron (MN), motor neuron diseases (MNDs), spinal cord (SpC), spinal cord organoids (SCOs), in vitro disease modeling, development, organoids

Library keywords