Impaired function of bone marrow stromal cells in systemic mastocytosis
| Autor: | Miklos Krepuska, Todd M. Wilson, David M. Stroncek, Eva Mezey, Yun Bai, Pamela Gehron Robey, Dean D. Metcalfe, Jiaqiang Ren, Krisztián Németh, Marianna Sabatino |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Stromal cell CD34 Bone Marrow Cells Biology Article Bone remodeling Colony-Forming Units Assay Mice Mastocytosis Systemic stomatognathic system Osteogenesis medicine Animals Humans Gene Regulatory Networks Systemic mastocytosis Cell Shape lcsh:QH301-705.5 Aged Cell Proliferation Medicine(all) Adipogenesis Gene Expression Profiling Mesenchymal stem cell hemic and immune systems General Medicine Cell Biology Middle Aged medicine.disease Tissue Donors Hematopoiesis Proto-Oncogene Proteins c-kit Haematopoiesis medicine.anatomical_structure lcsh:Biology (General) Case-Control Studies Mutation Immunology Cancer research Female Bone marrow Stromal Cells Stem cell Developmental Biology |
| Zdroj: | Stem Cell Research, Vol 15, Iss 1, Pp 42-53 (2015) |
| ISSN: | 1873-5061 |
| DOI: | 10.1016/j.scr.2015.04.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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