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Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical tr...

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Autores principales: Cao, Ting-Ting, Chen, Huan, Pang, Mao, Xu, Si-Si, Wen, Hui-Quan, Liu, Bin, Rong, Li-Min, Li, Mang-Mang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820722/
https://www.ncbi.nlm.nih.gov/pubmed/35017439
http://dx.doi.org/10.4103/1673-5374.332151
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author Cao, Ting-Ting
Chen, Huan
Pang, Mao
Xu, Si-Si
Wen, Hui-Quan
Liu, Bin
Rong, Li-Min
Li, Mang-Mang
author_facet Cao, Ting-Ting
Chen, Huan
Pang, Mao
Xu, Si-Si
Wen, Hui-Quan
Liu, Bin
Rong, Li-Min
Li, Mang-Mang
author_sort Cao, Ting-Ting
collection PubMed
description Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 10(6) hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs – low (0.25 × 10(6) cells/kg), medium (1 × 10(6) cells/kg) and high (4 × 10(6) cells/kg) – on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABA(A)) receptor expression by the effective doses indicates that GABA(A) receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 10(6) hUC-MSCs/kg is an alternative approach for treating subacute SCI.
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spelling pubmed-88207222022-02-24 Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury Cao, Ting-Ting Chen, Huan Pang, Mao Xu, Si-Si Wen, Hui-Quan Liu, Bin Rong, Li-Min Li, Mang-Mang Neural Regen Res Research Article Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 10(6) hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs – low (0.25 × 10(6) cells/kg), medium (1 × 10(6) cells/kg) and high (4 × 10(6) cells/kg) – on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABA(A)) receptor expression by the effective doses indicates that GABA(A) receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 10(6) hUC-MSCs/kg is an alternative approach for treating subacute SCI. Wolters Kluwer - Medknow 2022-01-07 /pmc/articles/PMC8820722/ /pubmed/35017439 http://dx.doi.org/10.4103/1673-5374.332151 Text en Copyright: © Neural Regeneration Research https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Cao, Ting-Ting
Chen, Huan
Pang, Mao
Xu, Si-Si
Wen, Hui-Quan
Liu, Bin
Rong, Li-Min
Li, Mang-Mang
Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury
title Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury
title_full Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury
title_fullStr Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury
title_full_unstemmed Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury
title_short Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury
title_sort dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820722/
https://www.ncbi.nlm.nih.gov/pubmed/35017439
http://dx.doi.org/10.4103/1673-5374.332151
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