Three-Dimensional Environment Sustains Hematopoietic Stem Cell Differentiation into Platelet-Producing Megakaryocytes
| Autor: | Dominique Baruch, Alexandre Kauskot, Didier Letourneur, Sophie Gandrille, Sonia Poirault-Chassac, Audrey Pietrzyk-Nivau, Sidi-Mohammed Derkaoui, Catherine Le Visage |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Blood Platelets
Male Cellular differentiation Science Integrin alpha2 Kruppel-Like Transcription Factors Antigens CD34 Biology Thrombopoiesis Proto-Oncogene Proteins c-myb 03 medical and health sciences 0302 clinical medicine Humans Platelet activation Progenitor cell Cells Cultured 030304 developmental biology Megakaryopoiesis 0303 health sciences Multidisciplinary Tissue Scaffolds Hematopoietic stem cell differentiation Integrin beta3 Cell Differentiation Hydrogels Hematopoietic Stem Cells Cell biology Haematopoiesis Gene Expression Regulation NF-E2 Transcription Factor p45 Subunit 030220 oncology & carcinogenesis Immunology Medicine Female Stem cell Megakaryocytes Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 8, p e0136652 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Hematopoietic stem cells (HSC) differentiate into megakaryocytes (MK), whose function is to release platelets. Attempts to improve in vitro platelet production have been hampered by the low amplification of MK. Providing HSC with an optimal three-dimensional (3D) architecture may favor MK differentiation by mimicking some crucial functions of the bone marrow structure. To this aim, porous hydrogel scaffolds were used to study MK differentiation from HSC as well as platelet production. Flow cytometry, qPCR and perfusion studies showed that 3D was suitable for longer kinetics of CD34+ cell proliferation and for delayed megakaryocytic differentiation far beyond the limited shelf-life observed in liquid culture but also increased production of functional platelets. We provide evidence that these 3D effects were related to 1) persistence of MK progenitors and precursors and 2) prolongation of expression of EKLF and c-myb transcription factors involved in early MK differentiation. In addition, presence of abundant mature MK with increased ploidy and impressive cytoskeleton elongations was in line with expression of NF-E2 transcription factor involved in late MK differentiation. Platelets produced in flow conditions were functional as shown by integrin αIIbβ3 activation following addition of exogenous agonists. This study demonstrates that spatial organization and biological cues synergize to improve MK differentiation and platelet production. Thus, 3D environment constitutes a powerful tool for unraveling the physiological mechanisms of megakaryopoiesis and thrombopoiesis in the bone marrow environment, potentially leading to an improved amplification of MK and platelet production. |
| Databáze: | OpenAIRE |
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