Neurochemical and Morphological Comparisons of Motor Nerve Organoids and Spinal-Cord Explants

Shannon E. Murphy; Amanda C. Sullivan-Weiss; Chen H. Sirois; Stanislav S. Rubakhin; Hyunjoon Kong; Martha U. Gillette; Jonathan V. Sweedler

doi:10.1021/acschemneuro.4c00625

Neurochemical and Morphological Comparisons of Motor Nerve Organoids and Spinal-Cord Explants

Shannon E. Murphy, Amanda C. Sullivan-Weiss, Chen H. Sirois, Stanislav S. Rubakhin, Hyunjoon Kong, Martha U. Gillette, Jonathan V. Sweedler

Research output: Contribution to journal › Article › peer-review

Abstract

Organoids are multicellular structures formed in vitro from populations of individual cells allowing modeling of structural and functional aspects of organs and tissues in normal and diseased states. They offer unique opportunities to model and treat disease. Using a mouse embryonic stem cell line, we have cultured organoids that express markers of spinal cord motor neurons as well as motor neurons found within the peripheral nervous system. The morphology and select neurotransmitter content of the organoids and spinal cord explants were compared at different developmental time points. We found indications of maturation in the organoids over time, mirrored by similar trends in the spinal cord explants. Although the organoids contained the same neurotransmitters as the spinal cord explants, the developmental changes of these neurotransmitter levels were less marked in organoids. Given these differences, further work is required to optimize organoid growth conditions to better reproduce in vivo models when using organoids to study development.

Original language	English (US)
Pages (from-to)	30-39
Number of pages	10
Journal	ACS Chemical Neuroscience
Volume	16
Issue number	1
DOIs	https://doi.org/10.1021/acschemneuro.4c00625
State	Published - Jan 2025

Keywords

capillary electrophoresis-mass spectrometry
development
morphology
neurotransmitter
organoid
spinal cord explants

ASJC Scopus subject areas

Biochemistry
Physiology
Cognitive Neuroscience
Cell Biology

Online availability

10.1021/acschemneuro.4c00625

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title = "Neurochemical and Morphological Comparisons of Motor Nerve Organoids and Spinal-Cord Explants",

abstract = "Organoids are multicellular structures formed in vitro from populations of individual cells allowing modeling of structural and functional aspects of organs and tissues in normal and diseased states. They offer unique opportunities to model and treat disease. Using a mouse embryonic stem cell line, we have cultured organoids that express markers of spinal cord motor neurons as well as motor neurons found within the peripheral nervous system. The morphology and select neurotransmitter content of the organoids and spinal cord explants were compared at different developmental time points. We found indications of maturation in the organoids over time, mirrored by similar trends in the spinal cord explants. Although the organoids contained the same neurotransmitters as the spinal cord explants, the developmental changes of these neurotransmitter levels were less marked in organoids. Given these differences, further work is required to optimize organoid growth conditions to better reproduce in vivo models when using organoids to study development.",

keywords = "capillary electrophoresis-mass spectrometry, development, morphology, neurotransmitter, organoid, spinal cord explants",

author = "Murphy, {Shannon E.} and Sullivan-Weiss, {Amanda C.} and Sirois, {Chen H.} and Rubakhin, {Stanislav S.} and Hyunjoon Kong and Gillette, {Martha U.} and Sweedler, {Jonathan V.}",

note = "We acknowledge support by Award Number P30 DA018310 from the National Institute on Drug Abuse (J.V.S.), the National Science Foundation under grant 1735252 (M.U.G., H.K., and J.V.S.), and an Accelerator grant from the Chan-Zuckerberg Biohub Chicago, LLC (H.K., M.U.G., and J.V.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The authors thank Roger Kamm (MIT) for the generous gift of H69-GFP-expressing mouse embryonic stem cells. We acknowledge support by Award Number P30 DA018310 from the National Institute on Drug Abuse (J.V.S.), the National Science Foundation under grant 1735252 (M.U.G., H.K., and J.V.S.), and an Accelerator grant from the Chan-Zuckerberg Biohub Chicago, LLC (H.K., M.U.G., and J.V.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.",

year = "2025",

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AU - Rubakhin, Stanislav S.

AU - Kong, Hyunjoon

AU - Gillette, Martha U.

AU - Sweedler, Jonathan V.

N1 - We acknowledge support by Award Number P30 DA018310 from the National Institute on Drug Abuse (J.V.S.), the National Science Foundation under grant 1735252 (M.U.G., H.K., and J.V.S.), and an Accelerator grant from the Chan-Zuckerberg Biohub Chicago, LLC (H.K., M.U.G., and J.V.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The authors thank Roger Kamm (MIT) for the generous gift of H69-GFP-expressing mouse embryonic stem cells. We acknowledge support by Award Number P30 DA018310 from the National Institute on Drug Abuse (J.V.S.), the National Science Foundation under grant 1735252 (M.U.G., H.K., and J.V.S.), and an Accelerator grant from the Chan-Zuckerberg Biohub Chicago, LLC (H.K., M.U.G., and J.V.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

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N2 - Organoids are multicellular structures formed in vitro from populations of individual cells allowing modeling of structural and functional aspects of organs and tissues in normal and diseased states. They offer unique opportunities to model and treat disease. Using a mouse embryonic stem cell line, we have cultured organoids that express markers of spinal cord motor neurons as well as motor neurons found within the peripheral nervous system. The morphology and select neurotransmitter content of the organoids and spinal cord explants were compared at different developmental time points. We found indications of maturation in the organoids over time, mirrored by similar trends in the spinal cord explants. Although the organoids contained the same neurotransmitters as the spinal cord explants, the developmental changes of these neurotransmitter levels were less marked in organoids. Given these differences, further work is required to optimize organoid growth conditions to better reproduce in vivo models when using organoids to study development.

AB - Organoids are multicellular structures formed in vitro from populations of individual cells allowing modeling of structural and functional aspects of organs and tissues in normal and diseased states. They offer unique opportunities to model and treat disease. Using a mouse embryonic stem cell line, we have cultured organoids that express markers of spinal cord motor neurons as well as motor neurons found within the peripheral nervous system. The morphology and select neurotransmitter content of the organoids and spinal cord explants were compared at different developmental time points. We found indications of maturation in the organoids over time, mirrored by similar trends in the spinal cord explants. Although the organoids contained the same neurotransmitters as the spinal cord explants, the developmental changes of these neurotransmitter levels were less marked in organoids. Given these differences, further work is required to optimize organoid growth conditions to better reproduce in vivo models when using organoids to study development.

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Neurochemical and Morphological Comparisons of Motor Nerve Organoids and Spinal-Cord Explants

Abstract

Keywords

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