LOTUS overexpression via ex vivo gene transduction further promotes recovery of motor function following human iPSC-NS/PC transplantation for contusive spinal cord injury.
Animals
Calcium-Binding Proteins
/ genetics
Cells, Cultured
Disease Models, Animal
Female
Gene Expression
Humans
Induced Pluripotent Stem Cells
/ metabolism
Mice, Inbred NOD
Mice, SCID
Motor Activity
/ physiology
Neural Stem Cells
/ metabolism
Recovery of Function
/ physiology
Spinal Cord
/ physiopathology
Spinal Cord Injuries
/ physiopathology
Stem Cell Transplantation
/ methods
Transduction, Genetic
Transplantation, Heterologous
LOTUS
Nogo receptor
axonal regrowth
ex vivo gene therapy
iPSC
motor function
regenerative medicine
spinal cord injury
transplantation
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
09 11 2021
09 11 2021
Historique:
received:
13
03
2021
revised:
13
09
2021
accepted:
14
09
2021
pubmed:
16
10
2021
medline:
15
3
2022
entrez:
15
10
2021
Statut:
ppublish
Résumé
Functional recovery is still limited mainly due to several mechanisms, such as the activation of Nogo receptor-1 (NgR1) signaling, when human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PC) are transplanted for subacute spinal cord injury (SCI). We previously reported the neuroprotective and regenerative benefits of overexpression of lateral olfactory tract usher substance (LOTUS), an endogenous NgR1 antagonist, in the injured spinal cord using transgenic mice. Here, we evaluate the effects of lentiviral transduction of LOTUS gene into hiPSC-NS/PCs before transplantation in a mouse model of subacute SCI. The transduced LOTUS contributes to neurite extension, suppression of apoptosis, and secretion of neurotrophic factors in vitro. In vivo, the hiPSC-NS/PCs enhance the survival of grafted cells and enhance axonal extension of the transplanted cells, resulting in significant restoration of motor function following SCI. Therefore, the gene transduction of LOTUS in hiPSC-NS/PCs could be a promising adjunct for transplantation therapy for SCI.
Identifiants
pubmed: 34653401
pii: S2213-6711(21)00482-3
doi: 10.1016/j.stemcr.2021.09.006
pmc: PMC8580872
pii:
doi:
Substances chimiques
Calcium-Binding Proteins
0
Crtac1 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2703-2717Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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