Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells
| Autor: | Veronique Lapostolle, Marija Vlaski-Lafarge, Pascale Duchez, Antonin Bourdieu, Jean Chevaleyre, Arnaud Villacreces, Zoran Ivanovic, Sadek Ismail, Philippe Brunet de la Grange, Christelle Debeissat, Maryse Avalon, Margaux Mombled, Marianne Guérinet, Vincent Praloran |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry Antigens CD34 Transfection Cell therapy Mice 03 medical and health sciences 0302 clinical medicine Side population Basic Helix-Loop-Helix Transcription Factors medicine Animals Humans Progenitor cell Clonogenic assay Side-Population Cells Cells Cultured Cell Proliferation Blood Cells Chemistry Hematopoietic Stem Cell Transplantation Cell Biology Fetal Blood Hematopoietic Stem Cells Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Mitochondria Cell biology Haematopoiesis Glucose Phenotype 030104 developmental biology medicine.anatomical_structure Cord blood Heterografts Female RNA Interference Bone marrow Stem cell Energy Metabolism Biomarkers 030215 immunology |
| Zdroj: | Journal of Cellular Physiology. 233:338-349 |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy. |
| Databáze: | OpenAIRE |
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