Cargando…

Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity

The therapeutic applications of mesenchymal stem cells (MSCs) have been actively explored due to their broad anti-inflammatory and immunomodulatory properties. However, the use of xenogeneic components, including fetal bovine serum (FBS), in the expansion media might pose a risk of xenoimmunization...

Descripción completa

Detalles Bibliográficos
Autores principales: Kang, Ji Yeon, Oh, Mi-Kyung, Joo, Hansol, Park, Hyun Sung, Chae, Dong-Hoon, Kim, Jieun, Lee, Hae-Ri, Oh, Il-Hoan, Yu, Kyung-Rok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565923/
https://www.ncbi.nlm.nih.gov/pubmed/32927587
http://dx.doi.org/10.3390/jcm9092913
_version_ 1783596039607943168
author Kang, Ji Yeon
Oh, Mi-Kyung
Joo, Hansol
Park, Hyun Sung
Chae, Dong-Hoon
Kim, Jieun
Lee, Hae-Ri
Oh, Il-Hoan
Yu, Kyung-Rok
author_facet Kang, Ji Yeon
Oh, Mi-Kyung
Joo, Hansol
Park, Hyun Sung
Chae, Dong-Hoon
Kim, Jieun
Lee, Hae-Ri
Oh, Il-Hoan
Yu, Kyung-Rok
author_sort Kang, Ji Yeon
collection PubMed
description The therapeutic applications of mesenchymal stem cells (MSCs) have been actively explored due to their broad anti-inflammatory and immunomodulatory properties. However, the use of xenogeneic components, including fetal bovine serum (FBS), in the expansion media might pose a risk of xenoimmunization and zoonotic transmission to post-transplanted patients. Here, we extensively compared the physiological functions of human Wharton’s jelly-derived MSCs (WJ-MSCs) in a xeno-free medium (XF-MSCs) and a medium containing 10% FBS (10%-MSCs). Both groups showed similar proliferation potential; however, the 10%-MSCs showed prolonged expression of CD146, with higher colony-forming unit-fibroblast (CFU-F) ability than the XF-MSCs. The XF-MSCs showed enhanced adipogenic differentiation potential and sufficient hematopoietic stem cell (HSC) niche activity, with elevated niche-related markers including CXCL12. Furthermore, we demonstrated that the XF-MSCs had a significantly higher suppressive effect on human peripheral blood-derived T cell proliferation, Th1 and Th17 differentiation, as well as naïve macrophage polarization toward an M1 phenotype. Among the anti-inflammatory molecules, the production of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase 2 (NOS2) was profoundly increased, whereas cyclooxygenase-2 (COX-2) was decreased in the XF-MSCs. Finally, the XF-MSCs had an enhanced therapeutic effect against mouse experimental colitis. These findings indicate that xeno-free culture conditions improved the immunomodulatory properties of WJ-MSCs and ex vivo-expanded XF-MSCs might be an effective strategy for preventing the progression of colitis.
format Online
Article
Text
id pubmed-7565923
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75659232020-10-26 Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity Kang, Ji Yeon Oh, Mi-Kyung Joo, Hansol Park, Hyun Sung Chae, Dong-Hoon Kim, Jieun Lee, Hae-Ri Oh, Il-Hoan Yu, Kyung-Rok J Clin Med Article The therapeutic applications of mesenchymal stem cells (MSCs) have been actively explored due to their broad anti-inflammatory and immunomodulatory properties. However, the use of xenogeneic components, including fetal bovine serum (FBS), in the expansion media might pose a risk of xenoimmunization and zoonotic transmission to post-transplanted patients. Here, we extensively compared the physiological functions of human Wharton’s jelly-derived MSCs (WJ-MSCs) in a xeno-free medium (XF-MSCs) and a medium containing 10% FBS (10%-MSCs). Both groups showed similar proliferation potential; however, the 10%-MSCs showed prolonged expression of CD146, with higher colony-forming unit-fibroblast (CFU-F) ability than the XF-MSCs. The XF-MSCs showed enhanced adipogenic differentiation potential and sufficient hematopoietic stem cell (HSC) niche activity, with elevated niche-related markers including CXCL12. Furthermore, we demonstrated that the XF-MSCs had a significantly higher suppressive effect on human peripheral blood-derived T cell proliferation, Th1 and Th17 differentiation, as well as naïve macrophage polarization toward an M1 phenotype. Among the anti-inflammatory molecules, the production of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase 2 (NOS2) was profoundly increased, whereas cyclooxygenase-2 (COX-2) was decreased in the XF-MSCs. Finally, the XF-MSCs had an enhanced therapeutic effect against mouse experimental colitis. These findings indicate that xeno-free culture conditions improved the immunomodulatory properties of WJ-MSCs and ex vivo-expanded XF-MSCs might be an effective strategy for preventing the progression of colitis. MDPI 2020-09-10 /pmc/articles/PMC7565923/ /pubmed/32927587 http://dx.doi.org/10.3390/jcm9092913 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kang, Ji Yeon
Oh, Mi-Kyung
Joo, Hansol
Park, Hyun Sung
Chae, Dong-Hoon
Kim, Jieun
Lee, Hae-Ri
Oh, Il-Hoan
Yu, Kyung-Rok
Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity
title Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity
title_full Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity
title_fullStr Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity
title_full_unstemmed Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity
title_short Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity
title_sort xeno-free condition enhances therapeutic functions of human wharton’s jelly-derived mesenchymal stem cells against experimental colitis by upregulated indoleamine 2,3-dioxygenase activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565923/
https://www.ncbi.nlm.nih.gov/pubmed/32927587
http://dx.doi.org/10.3390/jcm9092913
work_keys_str_mv AT kangjiyeon xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity
AT ohmikyung xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity
AT joohansol xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity
AT parkhyunsung xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity
AT chaedonghoon xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity
AT kimjieun xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity
AT leehaeri xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity
AT ohilhoan xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity
AT yukyungrok xenofreeconditionenhancestherapeuticfunctionsofhumanwhartonsjellyderivedmesenchymalstemcellsagainstexperimentalcolitisbyupregulatedindoleamine23dioxygenaseactivity