Format

Send to

Choose Destination
PLoS One. 2013 Jul 25;8(7):e69293. doi: 10.1371/journal.pone.0069293. Print 2013.

A prospective study of bone marrow hematopoietic and mesenchymal stem cells in type 1 Gaucher disease patients.

Author information

1
Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Unité de Thérapie Cellulaire et Centre d'Investigation Clinique en Biothérapies CIC-BT501, Paris, France.

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.

PMID:
23935976
PMCID:
PMC3723887
DOI:
10.1371/journal.pone.0069293
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center