Cargando…

The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis

BACKGROUND: ECBio has developed proprietary technology to consistently isolate, expand and cryopreserve a well-characterized population of stromal cells from human umbilical cord tissue (UCX® cells). The technology has recently been optimized in order to become compliant with Advanced Medicine Thera...

Descripción completa

Detalles Bibliográficos
Autores principales: Santos, Jorge M, Bárcia, Rita N, Simões, Sandra I, Gaspar, Manuela M, Calado, Susana, Água-Doce, Ana, Almeida, Sílvia CP, Almeida, Joana, Filipe, Mariana, Teixeira, Mariana, Martins, José P, Graça, Luís, Cruz, Maria EM, Cruz, Pedro, Cruz, Helder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561123/
https://www.ncbi.nlm.nih.gov/pubmed/23324136
http://dx.doi.org/10.1186/1479-5876-11-18
_version_ 1782257907501367296
author Santos, Jorge M
Bárcia, Rita N
Simões, Sandra I
Gaspar, Manuela M
Calado, Susana
Água-Doce, Ana
Almeida, Sílvia CP
Almeida, Joana
Filipe, Mariana
Teixeira, Mariana
Martins, José P
Graça, Luís
Cruz, Maria EM
Cruz, Pedro
Cruz, Helder
author_facet Santos, Jorge M
Bárcia, Rita N
Simões, Sandra I
Gaspar, Manuela M
Calado, Susana
Água-Doce, Ana
Almeida, Sílvia CP
Almeida, Joana
Filipe, Mariana
Teixeira, Mariana
Martins, José P
Graça, Luís
Cruz, Maria EM
Cruz, Pedro
Cruz, Helder
author_sort Santos, Jorge M
collection PubMed
description BACKGROUND: ECBio has developed proprietary technology to consistently isolate, expand and cryopreserve a well-characterized population of stromal cells from human umbilical cord tissue (UCX® cells). The technology has recently been optimized in order to become compliant with Advanced Medicine Therapeutic Products. In this work we report the immunosuppressive capacity of UCX® cells for treating induced autoimmune inflammatory arthritis. METHODS: UCX® cells were isolated using a proprietary method (PCT/IB2008/054067) that yields a well-defined number of cells using a precise proportion between tissue digestion enzyme activity units, tissue mass, digestion solution volume and void volume. The procedure includes three recovery steps to avoid non-conformities related to cell recovery. UCX® surface markers were characterized by flow cytometry and UCX® capacity to expand in vitro and to differentiate into adipocyte, chondrocyte and osteoblast-like cells was evaluated. Mixed Lymphocyte Reaction (MLR) assays were performed to evaluate the effect of UCX® cells on T-cell activation and Treg conversion assays were also performed in vitro. Furthermore, UCX® cells were administered in vivo in both a rat acute carrageenan-induced arthritis model and rat chronic adjuvant induced arthritis model for arthritic inflammation. UCX® anti-inflammatory activity was then monitored over time. RESULTS: UCX® cells stained positive for CD44, CD73, CD90 and CD105; and negative for CD14, CD19 CD31, CD34, CD45 and HLA-DR; and were capable to differentiate into adipocyte, chondrocyte and osteoblast-like cells. UCX® cells were shown to repress T-cell activation and promote the expansion of Tregs better than bone marrow mesenchymal stem cells (BM-MSCs). Accordingly, xenogeneic UCX® administration in an acute carrageenan-induced arthritis model showed that human UCX® cells can reduce paw edema in vivo more efficiently than BM-MSCs. Finally, in a chronic adjuvant induced arthritis model, animals treated with intra-articular (i.a.) and intra-peritoneal (i.p.) infusions of UCX® cells showed faster remission of local and systemic arthritic manifestations. CONCLUSION: The results suggest that UCX® cells may be an effective and promising new approach for treating both local and systemic manifestations of inflammatory arthritis.
format Online
Article
Text
id pubmed-3561123
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-35611232013-02-05 The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis Santos, Jorge M Bárcia, Rita N Simões, Sandra I Gaspar, Manuela M Calado, Susana Água-Doce, Ana Almeida, Sílvia CP Almeida, Joana Filipe, Mariana Teixeira, Mariana Martins, José P Graça, Luís Cruz, Maria EM Cruz, Pedro Cruz, Helder J Transl Med Research BACKGROUND: ECBio has developed proprietary technology to consistently isolate, expand and cryopreserve a well-characterized population of stromal cells from human umbilical cord tissue (UCX® cells). The technology has recently been optimized in order to become compliant with Advanced Medicine Therapeutic Products. In this work we report the immunosuppressive capacity of UCX® cells for treating induced autoimmune inflammatory arthritis. METHODS: UCX® cells were isolated using a proprietary method (PCT/IB2008/054067) that yields a well-defined number of cells using a precise proportion between tissue digestion enzyme activity units, tissue mass, digestion solution volume and void volume. The procedure includes three recovery steps to avoid non-conformities related to cell recovery. UCX® surface markers were characterized by flow cytometry and UCX® capacity to expand in vitro and to differentiate into adipocyte, chondrocyte and osteoblast-like cells was evaluated. Mixed Lymphocyte Reaction (MLR) assays were performed to evaluate the effect of UCX® cells on T-cell activation and Treg conversion assays were also performed in vitro. Furthermore, UCX® cells were administered in vivo in both a rat acute carrageenan-induced arthritis model and rat chronic adjuvant induced arthritis model for arthritic inflammation. UCX® anti-inflammatory activity was then monitored over time. RESULTS: UCX® cells stained positive for CD44, CD73, CD90 and CD105; and negative for CD14, CD19 CD31, CD34, CD45 and HLA-DR; and were capable to differentiate into adipocyte, chondrocyte and osteoblast-like cells. UCX® cells were shown to repress T-cell activation and promote the expansion of Tregs better than bone marrow mesenchymal stem cells (BM-MSCs). Accordingly, xenogeneic UCX® administration in an acute carrageenan-induced arthritis model showed that human UCX® cells can reduce paw edema in vivo more efficiently than BM-MSCs. Finally, in a chronic adjuvant induced arthritis model, animals treated with intra-articular (i.a.) and intra-peritoneal (i.p.) infusions of UCX® cells showed faster remission of local and systemic arthritic manifestations. CONCLUSION: The results suggest that UCX® cells may be an effective and promising new approach for treating both local and systemic manifestations of inflammatory arthritis. BioMed Central 2013-01-17 /pmc/articles/PMC3561123/ /pubmed/23324136 http://dx.doi.org/10.1186/1479-5876-11-18 Text en Copyright ©2013 Santos et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Santos, Jorge M
Bárcia, Rita N
Simões, Sandra I
Gaspar, Manuela M
Calado, Susana
Água-Doce, Ana
Almeida, Sílvia CP
Almeida, Joana
Filipe, Mariana
Teixeira, Mariana
Martins, José P
Graça, Luís
Cruz, Maria EM
Cruz, Pedro
Cruz, Helder
The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis
title The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis
title_full The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis
title_fullStr The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis
title_full_unstemmed The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis
title_short The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis
title_sort role of human umbilical cord tissue-derived mesenchymal stromal cells (ucx®) in the treatment of inflammatory arthritis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561123/
https://www.ncbi.nlm.nih.gov/pubmed/23324136
http://dx.doi.org/10.1186/1479-5876-11-18
work_keys_str_mv AT santosjorgem theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT barciaritan theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT simoessandrai theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT gasparmanuelam theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT caladosusana theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT aguadoceana theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT almeidasilviacp theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT almeidajoana theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT filipemariana theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT teixeiramariana theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT martinsjosep theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT gracaluis theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT cruzmariaem theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT cruzpedro theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT cruzhelder theroleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT santosjorgem roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT barciaritan roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT simoessandrai roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT gasparmanuelam roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT caladosusana roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT aguadoceana roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT almeidasilviacp roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT almeidajoana roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT filipemariana roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT teixeiramariana roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT martinsjosep roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT gracaluis roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT cruzmariaem roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT cruzpedro roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis
AT cruzhelder roleofhumanumbilicalcordtissuederivedmesenchymalstromalcellsucxinthetreatmentofinflammatoryarthritis