ArticlePloS one2015
Three-Dimensional Environment Sustains Hematopoietic Stem Cell Differentiation into Platelet-Producing Megakaryocytes.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Redox Regulation of Megakaryocyte Differentiation and Platelet Biogenesis.Antioxidants (Basel, Switzerland) · 2026Review
- Cell-based artificial platelet production: historical milestones, emerging trends, and future directions.Blood research · 2025Review
- Cellular crosstalk in the bone marrow niche.Journal of translational medicine · 2024Review
- An Innovative Inhibitor with a New Chemical Moiety Aimed at Biliverdin IXβ Reductase for Thrombocytopenia and Resilient against Cellular Degradation.Pharmaceutics · 2024Article
- Perfusion of MC3T3E1 Preosteoblast Spheroids within Polysaccharide-Based Hydrogel Scaffolds: An Experimental and Numerical Study at the Bioreactor Scale.Bioengineering (Basel, Switzerland) · 2023Article
- Inside-to-outside and back to the future of megakaryopoiesis.Research and practice in thrombosis and haemostasis · 2023Article
- Three-Dimensional Human Bone Marrow Organoids for the Study and Application of Normal and Abnormal Hematoimmunopoiesis.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Hydrogel-based microenvironment engineering of haematopoietic stem cells.Cellular and molecular life sciences : CMLS · 2023Review
- Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior.International journal of molecular sciences · 2022Article
- Tuning Physicochemical Properties of a Macroporous Polysaccharide-Based Scaffold for 3D Neuronal Culture.International journal of molecular sciences · 2021Article
- Latest culture techniques: cracking the secrets of bone marrow to mass-produce erythrocytes and plateletsHaematologica · 2021Review
- A comparison of haematopoietic stem cells from umbilical cord blood and peripheral blood for platelet production in a microfluidic device.Vox sanguinis · 2019Article
- Effect of cross-linking on the physicochemical and in vitro properties of pullulan/dextran microbeads.Journal of materials science. Materials in medicine · 2018Article
- Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells.Journal of the Royal Society, Interface · 2018Article
- Calf Spleen Extractive Injection protects mice against cyclophosphamide-induced hematopoietic injury through G-CSF-mediated JAK2/STAT3 signaling.Scientific reports · 2017Article
- Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint.Future science OA · 2017Review
- Recent developments in ex vivo platelet production.Cytotechnology · 2016Review
- LIM kinase/cofilin dysregulation promotes macrothrombocytopenia in severe von Willebrand disease-type 2B.JCI insight · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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