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A prospective study of bone marrow hematopoietic and mesenchymal stem cells in type 1 Gaucher disease patients
- Source :
- PLoS ONE, Vol 8, Iss 7, p e69293 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- 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.
- Subjects :
- Male
Cellular differentiation
Osteoclasts
lcsh:Medicine
Mice
Autosomal Recessive
Bone Marrow
Prospective Studies
Stem Cell Niche
lcsh:Science
Multidisciplinary
Hematology
Stem Cells
Cell Differentiation
Middle Aged
Adult Stem Cells
Haematopoiesis
Gaucher's disease
medicine.anatomical_structure
Cellular Microenvironment
Glucosylceramidase
Medicine
Female
Stem cell
Research Article
Adult
medicine.medical_specialty
Bone Marrow Cells
Biology
Internal medicine
Genetics
medicine
Animals
Humans
Progenitor cell
Aged
Cell Proliferation
Gaucher Disease
Osteoblasts
Mesenchymal stem cell
lcsh:R
Mesenchymal Stem Cells
Human Genetics
Hematopoietic Stem Cells
medicine.disease
Case-Control Studies
Immune System
Immunology
Clinical Immunology
lcsh:Q
Bone marrow
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....bb5ed22dfbb646666682cf6d125d50ce