What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?

MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of ly...

Full description

Saved in:
Bibliographic Details
Main Authors: R. N. Bárcia, J. M. Santos, M. Filipe, M. Teixeira, J. P. Martins, J. Almeida, A. Água-Doce, S. C. P. Almeida, A. Varela, S. Pohl, K. E. J. Dittmar, S. Calado, S. I. Simões, M. M. Gaspar, M. E. M. Cruz, W. Lindenmaier, L. Graça, H. Cruz, P. E. Cruz
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2015/583984
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832558290816466944
author R. N. Bárcia
J. M. Santos
M. Filipe
M. Teixeira
J. P. Martins
J. Almeida
A. Água-Doce
S. C. P. Almeida
A. Varela
S. Pohl
K. E. J. Dittmar
S. Calado
S. I. Simões
M. M. Gaspar
M. E. M. Cruz
W. Lindenmaier
L. Graça
H. Cruz
P. E. Cruz
author_facet R. N. Bárcia
J. M. Santos
M. Filipe
M. Teixeira
J. P. Martins
J. Almeida
A. Água-Doce
S. C. P. Almeida
A. Varela
S. Pohl
K. E. J. Dittmar
S. Calado
S. I. Simões
M. M. Gaspar
M. E. M. Cruz
W. Lindenmaier
L. Graça
H. Cruz
P. E. Cruz
author_sort R. N. Bárcia
collection DOAJ
description MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroborated in vivo in a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression of HLA-DRA, HO-1, IGFBP1, 4 and 6, ILR1, IL6R and PTGES and increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1β, IL-8, LIF and TGFβ2.
format Article
id doaj-art-0f4688eb33f44c479347f4d7395ed55c
institution Kabale University
issn 1687-966X
1687-9678
language English
publishDate 2015-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-0f4688eb33f44c479347f4d7395ed55c2025-02-03T01:32:42ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/583984583984What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?R. N. Bárcia0J. M. Santos1M. Filipe2M. Teixeira3J. P. Martins4J. Almeida5A. Água-Doce6S. C. P. Almeida7A. Varela8S. Pohl9K. E. J. Dittmar10S. Calado11S. I. Simões12M. M. Gaspar13M. E. M. Cruz14W. Lindenmaier15L. Graça16H. Cruz17P. E. Cruz18ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, PortugalECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, PortugalECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, PortugalECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, PortugalECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, PortugalECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, PortugalInstituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, PortugalInstituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, PortugalInstituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, PortugalHelmholtz Centre for Infection Research, Department of Gene Regulation and Differentiation, Inhoffenstaße 7, 38124 Braunschweig, GermanyHelmholtz Centre for Infection Research, Department of Gene Regulation and Differentiation, Inhoffenstaße 7, 38124 Braunschweig, GermanyResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, PortugalHelmholtz Centre for Infection Research, Department of Gene Regulation and Differentiation, Inhoffenstaße 7, 38124 Braunschweig, GermanyInstituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, PortugalECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, PortugalECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, PortugalMSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroborated in vivo in a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression of HLA-DRA, HO-1, IGFBP1, 4 and 6, ILR1, IL6R and PTGES and increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1β, IL-8, LIF and TGFβ2.http://dx.doi.org/10.1155/2015/583984
spellingShingle R. N. Bárcia
J. M. Santos
M. Filipe
M. Teixeira
J. P. Martins
J. Almeida
A. Água-Doce
S. C. P. Almeida
A. Varela
S. Pohl
K. E. J. Dittmar
S. Calado
S. I. Simões
M. M. Gaspar
M. E. M. Cruz
W. Lindenmaier
L. Graça
H. Cruz
P. E. Cruz
What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
Stem Cells International
title What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
title_full What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
title_fullStr What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
title_full_unstemmed What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
title_short What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
title_sort what makes umbilical cord tissue derived mesenchymal stromal cells superior immunomodulators when compared to bone marrow derived mesenchymal stromal cells
url http://dx.doi.org/10.1155/2015/583984
work_keys_str_mv AT rnbarcia whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT jmsantos whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT mfilipe whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT mteixeira whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT jpmartins whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT jalmeida whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT aaguadoce whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT scpalmeida whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT avarela whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT spohl whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT kejdittmar whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT scalado whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT sisimoes whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT mmgaspar whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT memcruz whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT wlindenmaier whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT lgraca whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT hcruz whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells
AT pecruz whatmakesumbilicalcordtissuederivedmesenchymalstromalcellssuperiorimmunomodulatorswhencomparedtobonemarrowderivedmesenchymalstromalcells