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A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients
Gaucher disease (GD) is an autosomal recessive disorder characterized by lysosomal glucocerebrosidase (GBA) deficiency leading to hematological and skeletal manifestations. Mechanisms underlying these symptoms have not yet been elucidated. In vivo, bone marrow (BM) mesenchymal stem cells (MSCs) have...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723887/ https://www.ncbi.nlm.nih.gov/pubmed/23935976 http://dx.doi.org/10.1371/journal.pone.0069293 |
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author | Lecourt, Séverine Mouly, Enguerran Freida, Delphine Cras, Audrey Ceccaldi, Raphaël Heraoui, Djazia Chomienne, Christine Marolleau, Jean-Pierre Arnulf, Bertrand Porcher, Raphael Caillaud, Catherine Vanneaux, Valérie Belmatoug, Nadia Larghero, Jérôme |
author_facet | Lecourt, Séverine Mouly, Enguerran Freida, Delphine Cras, Audrey Ceccaldi, Raphaël Heraoui, Djazia Chomienne, Christine Marolleau, Jean-Pierre Arnulf, Bertrand Porcher, Raphael Caillaud, Catherine Vanneaux, Valérie Belmatoug, Nadia Larghero, Jérôme |
author_sort | Lecourt, Séverine |
collection | PubMed |
description | Gaucher disease (GD) is an autosomal recessive disorder characterized by lysosomal glucocerebrosidase (GBA) deficiency leading to hematological and skeletal manifestations. Mechanisms underlying these symptoms have not yet been elucidated. In vivo, bone marrow (BM) mesenchymal stem cells (MSCs) have important role in the regulation of bone mass and in the support of hematopoiesis, thus representing potential candidate that could contribute to the disease. GBA deficiency may also directly impair hematopoietic stem/progenitors cells (HSPCs) intrinsic function and induce hematological defect. In order to evaluate the role of BM stem cells in GD pathophysiology, we prospectively analyzed BM-MSCs and HSPCs properties in a series of 10 patients with type 1 GD. GBA activity was decreased in all tested cell subtypes. GD-MSCs had an impaired growth potential, morphological and cell cycle abnormalities, decreased capacities to differentiate into osteoblasts. Moreover, GD-MSCs secreted soluble factors that stimulated osteoclasts resorbing activities. In vitro and in vivo primitive and mature hematopoiesis were similar between patients and controls. However, GD-MSCs had a lower hematopoietic supportive capacity than those from healthy donors. These data suggest that BM microenvironment is altered in GD and that MSCs are key components of the manifestations observed in GD. |
format | Online Article Text |
id | pubmed-3723887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37238872013-08-09 A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients Lecourt, Séverine Mouly, Enguerran Freida, Delphine Cras, Audrey Ceccaldi, Raphaël Heraoui, Djazia Chomienne, Christine Marolleau, Jean-Pierre Arnulf, Bertrand Porcher, Raphael Caillaud, Catherine Vanneaux, Valérie Belmatoug, Nadia Larghero, Jérôme PLoS One Research Article Gaucher disease (GD) is an autosomal recessive disorder characterized by lysosomal glucocerebrosidase (GBA) deficiency leading to hematological and skeletal manifestations. Mechanisms underlying these symptoms have not yet been elucidated. In vivo, bone marrow (BM) mesenchymal stem cells (MSCs) have important role in the regulation of bone mass and in the support of hematopoiesis, thus representing potential candidate that could contribute to the disease. GBA deficiency may also directly impair hematopoietic stem/progenitors cells (HSPCs) intrinsic function and induce hematological defect. In order to evaluate the role of BM stem cells in GD pathophysiology, we prospectively analyzed BM-MSCs and HSPCs properties in a series of 10 patients with type 1 GD. GBA activity was decreased in all tested cell subtypes. GD-MSCs had an impaired growth potential, morphological and cell cycle abnormalities, decreased capacities to differentiate into osteoblasts. Moreover, GD-MSCs secreted soluble factors that stimulated osteoclasts resorbing activities. In vitro and in vivo primitive and mature hematopoiesis were similar between patients and controls. However, GD-MSCs had a lower hematopoietic supportive capacity than those from healthy donors. These data suggest that BM microenvironment is altered in GD and that MSCs are key components of the manifestations observed in GD. Public Library of Science 2013-07-25 /pmc/articles/PMC3723887/ /pubmed/23935976 http://dx.doi.org/10.1371/journal.pone.0069293 Text en © 2013 Lecourt et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lecourt, Séverine Mouly, Enguerran Freida, Delphine Cras, Audrey Ceccaldi, Raphaël Heraoui, Djazia Chomienne, Christine Marolleau, Jean-Pierre Arnulf, Bertrand Porcher, Raphael Caillaud, Catherine Vanneaux, Valérie Belmatoug, Nadia Larghero, Jérôme A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients |
title | A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients |
title_full | A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients |
title_fullStr | A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients |
title_full_unstemmed | A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients |
title_short | A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients |
title_sort | prospective study of bone marrow hematopoietic and mesenchymal stem cells in type 1 gaucher disease patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723887/ https://www.ncbi.nlm.nih.gov/pubmed/23935976 http://dx.doi.org/10.1371/journal.pone.0069293 |
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