Impaired function of bone marrow stromal cells in systemic mastocytosis
Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem...
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doaj-d9d779c3f37d4b3bab2c50be8aaf23c22020-11-24T22:17:51ZengElsevierStem Cell Research1873-50611876-77532015-07-01151425310.1016/j.scr.2015.04.005Impaired function of bone marrow stromal cells in systemic mastocytosisKrisztian Nemeth0Todd M. Wilson1Jiaqiang J. Ren2Marianna Sabatino3David M. Stroncek4Miklos Krepuska5Yun Bai6Pamela G. Robey7Dean D. Metcalfe8Eva Mezey9Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USALaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USADepartment of Transfusion Medicine, Clinical Center, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USADepartment of Transfusion Medicine, Clinical Center, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USADepartment of Transfusion Medicine, Clinical Center, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USACraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USALaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USACraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USALaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USACraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USAPatients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34+ hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients.http://www.sciencedirect.com/science/article/pii/S1873506115000471 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Krisztian Nemeth Todd M. Wilson Jiaqiang J. Ren Marianna Sabatino David M. Stroncek Miklos Krepuska Yun Bai Pamela G. Robey Dean D. Metcalfe Eva Mezey |
spellingShingle |
Krisztian Nemeth Todd M. Wilson Jiaqiang J. Ren Marianna Sabatino David M. Stroncek Miklos Krepuska Yun Bai Pamela G. Robey Dean D. Metcalfe Eva Mezey Impaired function of bone marrow stromal cells in systemic mastocytosis Stem Cell Research |
author_facet |
Krisztian Nemeth Todd M. Wilson Jiaqiang J. Ren Marianna Sabatino David M. Stroncek Miklos Krepuska Yun Bai Pamela G. Robey Dean D. Metcalfe Eva Mezey |
author_sort |
Krisztian Nemeth |
title |
Impaired function of bone marrow stromal cells in systemic mastocytosis |
title_short |
Impaired function of bone marrow stromal cells in systemic mastocytosis |
title_full |
Impaired function of bone marrow stromal cells in systemic mastocytosis |
title_fullStr |
Impaired function of bone marrow stromal cells in systemic mastocytosis |
title_full_unstemmed |
Impaired function of bone marrow stromal cells in systemic mastocytosis |
title_sort |
impaired function of bone marrow stromal cells in systemic mastocytosis |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 1876-7753 |
publishDate |
2015-07-01 |
description |
Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34+ hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients. |
url |
http://www.sciencedirect.com/science/article/pii/S1873506115000471 |
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