Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, due to an immune reaction against myelin proteins. Multipotent mesenchymal stromal cells (MSCs) present immunosuppressive effects and have been used for the treatment of autoimmune diseases. In our st...
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Format: | Article |
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SAGE Publishing
2015-02-01
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Series: | Cell Transplantation |
Online Access: | https://doi.org/10.3727/096368913X675142 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gislane L. V. De Oliveira Ph.D. Kalil W. A. De Lima Amanda M. Colombini Daniel G. Pinheiro Rodrigo A. Panepucci Patrícia V. B. Palma Doralina G. Brum Dimas T. Covas Belinda P. Simões Maria C. De Oliveira Eduardo A. Donadi Kelen C. R. Malmegrim |
spellingShingle |
Gislane L. V. De Oliveira Ph.D. Kalil W. A. De Lima Amanda M. Colombini Daniel G. Pinheiro Rodrigo A. Panepucci Patrícia V. B. Palma Doralina G. Brum Dimas T. Covas Belinda P. Simões Maria C. De Oliveira Eduardo A. Donadi Kelen C. R. Malmegrim Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts Cell Transplantation |
author_facet |
Gislane L. V. De Oliveira Ph.D. Kalil W. A. De Lima Amanda M. Colombini Daniel G. Pinheiro Rodrigo A. Panepucci Patrícia V. B. Palma Doralina G. Brum Dimas T. Covas Belinda P. Simões Maria C. De Oliveira Eduardo A. Donadi Kelen C. R. Malmegrim |
author_sort |
Gislane L. V. De Oliveira Ph.D. |
title |
Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts |
title_short |
Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts |
title_full |
Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts |
title_fullStr |
Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts |
title_full_unstemmed |
Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts |
title_sort |
bone marrow mesenchymal stromal cells isolated from multiple sclerosis patients have distinct gene expression profile and decreased suppressive function compared with healthy counterparts |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2015-02-01 |
description |
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, due to an immune reaction against myelin proteins. Multipotent mesenchymal stromal cells (MSCs) present immunosuppressive effects and have been used for the treatment of autoimmune diseases. In our study, gene expression profile and in vitro immunomodulatory function tests were used to compare bone marrow-derived MSCs obtained from MS patients, at pre- and postautologous hematopoietic stem cell transplantation (AHSCT) with those from healthy donors. Patient MSCs comparatively exhibited i) senescence in culture; ii) similar osteogenic and adipogenic differentiation potential; iii) decreased expression of CD105, CD73, CD44, and HLA-A/B/C molecules; iv) distinct transcription at pre-AHSCT compared with control MSCs, yielding 618 differentially expressed genes, including the downregulation of TGFB1 and HGF genes and modulation of the FGF and HGF signaling pathways; v) reduced antiproliferative effects when pre-AHSCT MSCs were cocultured with allogeneic T-lymphocytes; vi) decreased secretion of IL-10 and TGF-β in supernatants of both cocultures (pre- and post-AHSCT MSCs); and vii) similar percentages of regulatory cells recovered after MSC cocultures. The transcriptional profile of patient MSCs isolated 6 months posttransplantation was closer to pre-AHSCT samples than from healthy MSCs. Considering that patient MSCs exhibited phenotypic changes, distinct transcriptional profile and functional defects implicated in MSC immunomodulatory and immunosuppressive activity, we suggest that further MS clinical studies should be conducted using allogeneic bone marrow MSCs derived from healthy donors. We also demonstrated that treatment of MS patients with AHSCT does not reverse the transcriptional and functional alterations observed in patient MSCs. |
url |
https://doi.org/10.3727/096368913X675142 |
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doaj-646b6ddaab764dba9addd12d4cf4462e2020-11-25T03:32:21ZengSAGE PublishingCell Transplantation0963-68971555-38922015-02-012410.3727/096368913X675142Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy CounterpartsGislane L. V. De Oliveira Ph.D.0Kalil W. A. De Lima1Amanda M. Colombini2Daniel G. Pinheiro3Rodrigo A. Panepucci4Patrícia V. B. Palma5Doralina G. Brum6Dimas T. Covas7Belinda P. Simões8Maria C. De Oliveira9Eduardo A. Donadi10Kelen C. R. Malmegrim11 Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Center for Cell-Based Research, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Center for Cell-Based Research, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Center for Cell-Based Research, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Center for Cell-Based Research, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Department of Neurology, Psychology and Psychiatry, School of Medicine of Botucatu, University of State of São Paulo (UNESP), Botucatu, São Paulo, Brazil Department of Clinical Medicine, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Department of Clinical Medicine, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Department of Clinical Medicine, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Department of Clinical Medicine, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, BrazilMultiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, due to an immune reaction against myelin proteins. Multipotent mesenchymal stromal cells (MSCs) present immunosuppressive effects and have been used for the treatment of autoimmune diseases. In our study, gene expression profile and in vitro immunomodulatory function tests were used to compare bone marrow-derived MSCs obtained from MS patients, at pre- and postautologous hematopoietic stem cell transplantation (AHSCT) with those from healthy donors. Patient MSCs comparatively exhibited i) senescence in culture; ii) similar osteogenic and adipogenic differentiation potential; iii) decreased expression of CD105, CD73, CD44, and HLA-A/B/C molecules; iv) distinct transcription at pre-AHSCT compared with control MSCs, yielding 618 differentially expressed genes, including the downregulation of TGFB1 and HGF genes and modulation of the FGF and HGF signaling pathways; v) reduced antiproliferative effects when pre-AHSCT MSCs were cocultured with allogeneic T-lymphocytes; vi) decreased secretion of IL-10 and TGF-β in supernatants of both cocultures (pre- and post-AHSCT MSCs); and vii) similar percentages of regulatory cells recovered after MSC cocultures. The transcriptional profile of patient MSCs isolated 6 months posttransplantation was closer to pre-AHSCT samples than from healthy MSCs. Considering that patient MSCs exhibited phenotypic changes, distinct transcriptional profile and functional defects implicated in MSC immunomodulatory and immunosuppressive activity, we suggest that further MS clinical studies should be conducted using allogeneic bone marrow MSCs derived from healthy donors. We also demonstrated that treatment of MS patients with AHSCT does not reverse the transcriptional and functional alterations observed in patient MSCs.https://doi.org/10.3727/096368913X675142 |