The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem c...

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Autores principales: Jin Hyoung Cho, Won Seok Ju, Sang Young Seo, Bo Hyun Kim, Ji-Su Kim, Jong-Geol Kim, Soon Ju Park, Young-Kug Choo
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:fe8af7c9e55942bbac7c61a1bfda804a2021-11-25T17:54:12ZThe Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor10.3390/ijms2222121941422-00671661-6596https://doaj.org/article/fe8af7c9e55942bbac7c61a1bfda804a2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12194https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.Jin Hyoung ChoWon Seok JuSang Young SeoBo Hyun KimJi-Su KimJong-Geol KimSoon Ju ParkYoung-Kug ChooMDPI AGarticlemacrophageminiature pig adipose tissue-derived mesenchymal stem cellsnanobodynucleoside diphosphate kinase AST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12194, p 12194 (2021)
institution DOAJ
collection DOAJ
language EN
topic macrophage
miniature pig adipose tissue-derived mesenchymal stem cells
nanobody
nucleoside diphosphate kinase A
ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle macrophage
miniature pig adipose tissue-derived mesenchymal stem cells
nanobody
nucleoside diphosphate kinase A
ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1
Biology (General)
QH301-705.5
Chemistry
QD1-999
Jin Hyoung Cho
Won Seok Ju
Sang Young Seo
Bo Hyun Kim
Ji-Su Kim
Jong-Geol Kim
Soon Ju Park
Young-Kug Choo
The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor
description This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.
format article
author Jin Hyoung Cho
Won Seok Ju
Sang Young Seo
Bo Hyun Kim
Ji-Su Kim
Jong-Geol Kim
Soon Ju Park
Young-Kug Choo
author_facet Jin Hyoung Cho
Won Seok Ju
Sang Young Seo
Bo Hyun Kim
Ji-Su Kim
Jong-Geol Kim
Soon Ju Park
Young-Kug Choo
author_sort Jin Hyoung Cho
title The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor
title_short The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor
title_full The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor
title_fullStr The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor
title_full_unstemmed The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor
title_sort potential role of human nme1 in neuronal differentiation of porcine mesenchymal stem cells: application of nb-hnme1 as a human nme1 suppressor
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/fe8af7c9e55942bbac7c61a1bfda804a
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