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Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons

Martinez-Curiel, Raquel LU orcid ; Jansson, Linda LU ; Tsupykov, Oleg ; Avaliani, Natalia LU ; Aretio-Medina, Constanza LU orcid ; Hidalgo, Isabel LU orcid ; Monni, Emanuela LU ; Bengzon, Johan LU ; Skibo, Galyna and Lindvall, Olle LU , et al. (2023) In Stem Cell Reports 18(8). p.1643-1656
Abstract

Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here, we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical... (More)

Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here, we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that, after intracerebral delivery, can repair both injured neural circuitries and demyelinated axons. Our findings provide supportive evidence for the potential future use of human iPSC-derived cell lines to promote effective clinical recovery following brain injuries.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cell therapy, Demyelination, Human brain, iPS cells, Myelin, Oligodendrocyte, Oligodendrogenesis, Remyelination, Stroke
in
Stem Cell Reports
volume
18
issue
8
pages
14 pages
publisher
Cell Press
external identifiers
  • pmid:37236198
  • scopus:85164805895
ISSN
2213-6711
DOI
10.1016/j.stemcr.2023.04.010
language
English
LU publication?
yes
id
99df6f61-6130-4c92-b4b1-7ae2ffb36869
date added to LUP
2023-10-06 13:04:44
date last changed
2024-04-19 02:00:39
@article{99df6f61-6130-4c92-b4b1-7ae2ffb36869,
  abstract     = {{<p>Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here, we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that, after intracerebral delivery, can repair both injured neural circuitries and demyelinated axons. Our findings provide supportive evidence for the potential future use of human iPSC-derived cell lines to promote effective clinical recovery following brain injuries.</p>}},
  author       = {{Martinez-Curiel, Raquel and Jansson, Linda and Tsupykov, Oleg and Avaliani, Natalia and Aretio-Medina, Constanza and Hidalgo, Isabel and Monni, Emanuela and Bengzon, Johan and Skibo, Galyna and Lindvall, Olle and Kokaia, Zaal and Palma-Tortosa, Sara}},
  issn         = {{2213-6711}},
  keywords     = {{Cell therapy; Demyelination; Human brain; iPS cells; Myelin; Oligodendrocyte; Oligodendrogenesis; Remyelination; Stroke}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1643--1656}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2023.04.010}},
  doi          = {{10.1016/j.stemcr.2023.04.010}},
  volume       = {{18}},
  year         = {{2023}},
}