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Multiple therapeutic effects of human neural stem cells derived from induced pluripotent stem cells in a rat model of post-traumatic syringomyelia

Xu, Tingting ; Li, Xiaofei ; Guo, Yuxi ; Uhlin, Elias LU ; Holmberg, Lena ; Mitra, Sumonto ; Winn, Dania LU ; Falk, Anna LU and Sundström, Erik (2022) In EBioMedicine 77.
Abstract

BACKGROUND: Post-traumatic syringomyelia (PTS) affects patients with chronic spinal cord injury (SCI) and is characterized by progressive deterioration of neurological symptoms. To improve surgical treatment, we studied the therapeutic effects of neuroepithelial-like stem cells (NESCs) derived from induced pluripotent stem cells (iPSCs) in a rat model of PTS. To facilitate clinical translation, we studied NESCs derived from Good Manufacturing Practice (GMP)-compliant iPSCs.

METHODS: Human GMP-compliant iPSCs were used to derive NESCs. Cryo-preserved NESCs were used off-the-shelf for intraspinal implantation to PTS rats 1 or 10 weeks post-injury, and rats were sacrificed 10 weeks later. In vivo cyst volumes were measured with... (More)

BACKGROUND: Post-traumatic syringomyelia (PTS) affects patients with chronic spinal cord injury (SCI) and is characterized by progressive deterioration of neurological symptoms. To improve surgical treatment, we studied the therapeutic effects of neuroepithelial-like stem cells (NESCs) derived from induced pluripotent stem cells (iPSCs) in a rat model of PTS. To facilitate clinical translation, we studied NESCs derived from Good Manufacturing Practice (GMP)-compliant iPSCs.

METHODS: Human GMP-compliant iPSCs were used to derive NESCs. Cryo-preserved NESCs were used off-the-shelf for intraspinal implantation to PTS rats 1 or 10 weeks post-injury, and rats were sacrificed 10 weeks later. In vivo cyst volumes were measured with micro-MRI. Phenotypes of differentiated NESCs and host responses were analyzed by immunohistochemistry.

FINDINGS: Off-the-shelf NESCs transplanted to PTS rats 10 weeks post-injury reduced cyst volume. The grafted NESCs differentiated mainly into glial cells. Importantly, NESCs also stimulated tissue repair. They reduced the density of glial scars and neurite-inhibiting chondroitin sulfate proteoglycan 4 (CSPG4), stimulated host oligodendrocyte precursor cells to migrate and proliferate, reduced active microglia/macrophages, and promoted axonal regrowth after subacute as well as chronic transplantation.

INTERPRETATION: Significant neural repair promoted by NESCs demonstrated that human NESCs could be used as a complement to standard surgery in PTS. We envisage that future PTS patients transplanted with NESCs will benefit both from eliminating the symptoms of PTS, as well as a long-term improvement of the neurological symptoms of SCI.

FUNDING: This work was supported by Vinnova (2016-04134), Karolinska Institutet StratRegen, and the Chinese Scholarship Council.

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; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Cell Differentiation, Humans, Induced Pluripotent Stem Cells/transplantation, Neural Stem Cells, Rats, Spinal Cord Injuries/complications, Syringomyelia/etiology
in
EBioMedicine
volume
77
article number
103882
publisher
Elsevier
external identifiers
  • pmid:35182996
  • scopus:85124608364
ISSN
2352-3964
DOI
10.1016/j.ebiom.2022.103882
language
English
LU publication?
no
additional info
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
id
5905394e-006e-49e4-94d0-058dd336b12e
date added to LUP
2022-09-20 14:12:37
date last changed
2024-06-14 23:40:32
@article{5905394e-006e-49e4-94d0-058dd336b12e,
  abstract     = {{<p>BACKGROUND: Post-traumatic syringomyelia (PTS) affects patients with chronic spinal cord injury (SCI) and is characterized by progressive deterioration of neurological symptoms. To improve surgical treatment, we studied the therapeutic effects of neuroepithelial-like stem cells (NESCs) derived from induced pluripotent stem cells (iPSCs) in a rat model of PTS. To facilitate clinical translation, we studied NESCs derived from Good Manufacturing Practice (GMP)-compliant iPSCs.</p><p>METHODS: Human GMP-compliant iPSCs were used to derive NESCs. Cryo-preserved NESCs were used off-the-shelf for intraspinal implantation to PTS rats 1 or 10 weeks post-injury, and rats were sacrificed 10 weeks later. In vivo cyst volumes were measured with micro-MRI. Phenotypes of differentiated NESCs and host responses were analyzed by immunohistochemistry.</p><p>FINDINGS: Off-the-shelf NESCs transplanted to PTS rats 10 weeks post-injury reduced cyst volume. The grafted NESCs differentiated mainly into glial cells. Importantly, NESCs also stimulated tissue repair. They reduced the density of glial scars and neurite-inhibiting chondroitin sulfate proteoglycan 4 (CSPG4), stimulated host oligodendrocyte precursor cells to migrate and proliferate, reduced active microglia/macrophages, and promoted axonal regrowth after subacute as well as chronic transplantation.</p><p>INTERPRETATION: Significant neural repair promoted by NESCs demonstrated that human NESCs could be used as a complement to standard surgery in PTS. We envisage that future PTS patients transplanted with NESCs will benefit both from eliminating the symptoms of PTS, as well as a long-term improvement of the neurological symptoms of SCI.</p><p>FUNDING: This work was supported by Vinnova (2016-04134), Karolinska Institutet StratRegen, and the Chinese Scholarship Council.</p>}},
  author       = {{Xu, Tingting and Li, Xiaofei and Guo, Yuxi and Uhlin, Elias and Holmberg, Lena and Mitra, Sumonto and Winn, Dania and Falk, Anna and Sundström, Erik}},
  issn         = {{2352-3964}},
  keywords     = {{Animals; Cell Differentiation; Humans; Induced Pluripotent Stem Cells/transplantation; Neural Stem Cells; Rats; Spinal Cord Injuries/complications; Syringomyelia/etiology}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{EBioMedicine}},
  title        = {{Multiple therapeutic effects of human neural stem cells derived from induced pluripotent stem cells in a rat model of post-traumatic syringomyelia}},
  url          = {{http://dx.doi.org/10.1016/j.ebiom.2022.103882}},
  doi          = {{10.1016/j.ebiom.2022.103882}},
  volume       = {{77}},
  year         = {{2022}},
}