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Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes

Chronic neuropathic pain is caused by dysfunction of the peripheral nerves associated with the somatosensory system. Mesenchymal stem cells (MSCs) have attracted attention as promising cell therapeutics for chronic pain; however, their clinical application has been hampered by the poor in vivo survi...

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Autores principales: Lee, Nayeon, Park, Gyu Tae, Lim, Jae Kyung, Choi, Eun Bae, Moon, Hye Ji, Kim, Dae Kyoung, Choi, Seong Min, Song, Young Cheol, Kim, Tae Kyun, Kim, Jae Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393760/
https://www.ncbi.nlm.nih.gov/pubmed/36003384
http://dx.doi.org/10.3389/fimmu.2022.940258
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author Lee, Nayeon
Park, Gyu Tae
Lim, Jae Kyung
Choi, Eun Bae
Moon, Hye Ji
Kim, Dae Kyoung
Choi, Seong Min
Song, Young Cheol
Kim, Tae Kyun
Kim, Jae Ho
author_facet Lee, Nayeon
Park, Gyu Tae
Lim, Jae Kyung
Choi, Eun Bae
Moon, Hye Ji
Kim, Dae Kyoung
Choi, Seong Min
Song, Young Cheol
Kim, Tae Kyun
Kim, Jae Ho
author_sort Lee, Nayeon
collection PubMed
description Chronic neuropathic pain is caused by dysfunction of the peripheral nerves associated with the somatosensory system. Mesenchymal stem cells (MSCs) have attracted attention as promising cell therapeutics for chronic pain; however, their clinical application has been hampered by the poor in vivo survival and low therapeutic efficacy of transplanted cells. Increasing evidence suggests enhanced therapeutic efficacy of spheroids formed by three-dimensional culture of MSCs. In the present study, we established a neuropathic pain murine model by inducing a chronic constriction injury through ligation of the right sciatic nerve and measured the therapeutic effects and survival efficacy of spheroids. Monolayer-cultured and spheroids were transplanted into the gastrocnemius muscle close to the damaged sciatic nerve. Transplantation of spheroids alleviated chronic pain more potently and exhibited prolonged in vivo survival compared to monolayer-cultured cells. Moreover, spheroids significantly reduced macrophage infiltration into the injured tissues. Interestingly, the expression of mouse-origin genes associated with inflammatory responses, Ccl11/Eotaxin, interleukin 1A, tumor necrosis factor B, and tumor necrosis factor, was significantly attenuated by the administration of spheroids compared to that of monolayer. These results suggest that MSC spheroids exhibit enhanced in vivo survival after cell transplantation and reduced the host inflammatory response through the regulation of main chronic inflammatory response-related genes.
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spelling pubmed-93937602022-08-23 Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes Lee, Nayeon Park, Gyu Tae Lim, Jae Kyung Choi, Eun Bae Moon, Hye Ji Kim, Dae Kyoung Choi, Seong Min Song, Young Cheol Kim, Tae Kyun Kim, Jae Ho Front Immunol Immunology Chronic neuropathic pain is caused by dysfunction of the peripheral nerves associated with the somatosensory system. Mesenchymal stem cells (MSCs) have attracted attention as promising cell therapeutics for chronic pain; however, their clinical application has been hampered by the poor in vivo survival and low therapeutic efficacy of transplanted cells. Increasing evidence suggests enhanced therapeutic efficacy of spheroids formed by three-dimensional culture of MSCs. In the present study, we established a neuropathic pain murine model by inducing a chronic constriction injury through ligation of the right sciatic nerve and measured the therapeutic effects and survival efficacy of spheroids. Monolayer-cultured and spheroids were transplanted into the gastrocnemius muscle close to the damaged sciatic nerve. Transplantation of spheroids alleviated chronic pain more potently and exhibited prolonged in vivo survival compared to monolayer-cultured cells. Moreover, spheroids significantly reduced macrophage infiltration into the injured tissues. Interestingly, the expression of mouse-origin genes associated with inflammatory responses, Ccl11/Eotaxin, interleukin 1A, tumor necrosis factor B, and tumor necrosis factor, was significantly attenuated by the administration of spheroids compared to that of monolayer. These results suggest that MSC spheroids exhibit enhanced in vivo survival after cell transplantation and reduced the host inflammatory response through the regulation of main chronic inflammatory response-related genes. Frontiers Media S.A. 2022-08-08 /pmc/articles/PMC9393760/ /pubmed/36003384 http://dx.doi.org/10.3389/fimmu.2022.940258 Text en Copyright © 2022 Lee, Park, Lim, Choi, Moon, Kim, Choi, Song, Kim and Kim https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lee, Nayeon
Park, Gyu Tae
Lim, Jae Kyung
Choi, Eun Bae
Moon, Hye Ji
Kim, Dae Kyoung
Choi, Seong Min
Song, Young Cheol
Kim, Tae Kyun
Kim, Jae Ho
Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes
title Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes
title_full Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes
title_fullStr Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes
title_full_unstemmed Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes
title_short Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes
title_sort mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393760/
https://www.ncbi.nlm.nih.gov/pubmed/36003384
http://dx.doi.org/10.3389/fimmu.2022.940258
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