ArticleStem cells translational medicine2015
Efficient generation of megakaryocytes from human induced pluripotent stem cells using food and drug administration-approved pharmacological reagents.
Article in Stem cells translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- Immunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms.Haematologica · 2026Article
- Laboratory Assessment and Clinical Outlook forAnnals of laboratory medicine · 2026Review
- Optimizing the Method for Differentiation of Functional Platelets from Human Induced Pluripotent Stem Cells.Stem cell reviews and reports · 2026Article
- Protocol for generating megakaryocytes from patient induced pluripotent stem cells for disease modeling and compound screening.STAR protocols · 2026Article
- DNA methyltransferase Dnmt3ba-mediated epigenetic modulation of Integrin signaling is essential for hematopoietic stem and progenitor cell development.Communications biology · 2025Article
- Cell-based artificial platelet production: historical milestones, emerging trends, and future directions.Blood research · 2025Review
- The winding road to platelet α-granules.Frontiers in cell and developmental biology · 2025Review
- Stem Cell Niche: iPSC-Based Assembloids for Modeling Human Hematopoiesis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The effect of decitabine on human induced pluripotent stem cells (hiPSCs) derived CD34American journal of stem cells · 2025Article
- Long-lived lung megakaryocytes contribute to platelet recovery in thrombocytopenia models.The Journal of clinical investigation · 2024Article
- Oncogenic Calreticulin Induces Immune Escape by Stimulating TGFβ Expression and Regulatory T-cell Expansion in the Bone Marrow Microenvironment.Cancer research · 2024Article
- Proinflammatory phenotype of iPS cell-derived JAK2 V617F megakaryocytes induces fibrosis in 3D in vitro bone marrow niche.Stem cell reports · 2024Article
- Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms.Cell reports · 2024Article
- Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges.Cell regeneration (London, England) · 2023Review
- Activation of lineage competence in hemogenic endothelium precedes the formation of hematopoietic stem cell heterogeneity.Cell research · 2023Article
- Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells.Cell discovery · 2022Article
- Towards personalized medicine with iPS cell technology: a case report of advanced systemic mastocytosis with associated eosinophilia.Annals of hematology · 2022Article
- Toward in Vitro Production of Platelet from Induced Pluripotent Stem Cells.Stem cell reviews and reports · 2022Review
- Hematopoietic differentiation persists in human iPSCs defective in de novo DNA methylation.BMC biology · 2022Article
- Megakaryocytes as the Regulator of the Hematopoietic Vascular Niche.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Megakaryocytes (MKs) are rare hematopoietic cells in the adult bone marrow and produce platelets that are critical to vascular hemostasis and wound healing. Ex vivo generation of MKs from human induced pluripotent stem cells (hiPSCs) provides a renewable cell source of platelets for treating thrombocytopenic patients and allows a better understanding of MK/platelet biology. The key requirements in this approach include developing a robust and consistent method to produce functional progeny cells, such as MKs from hiPSCs, and minimizing the risk and variation from the animal-derived products in cell cultures. In this study, we developed an efficient system to generate MKs from hiPSCs under a feeder-free and xeno-free condition, in which all animal-derived products were eliminated. Several crucial reagents were evaluated and replaced with Food and Drug Administration-approved pharmacological reagents, including romiplostim (Nplate, a thrombopoietin analog), oprelvekin (recombinant interleukin-11), and Plasbumin (human albumin). We used this method to induce MK generation from hiPSCs derived from 23 individuals in two steps: generation of CD34(+)CD45(+) hematopoietic progenitor cells (HPCs) for 14 days; and generation and expansion of CD41(+)CD42a(+) MKs from HPCs for an additional 5 days. After 19 days, we observed abundant CD41(+)CD42a(+) MKs that also expressed the MK markers CD42b and CD61 and displayed polyploidy (≥16% of derived cells with DNA contents >4N). Transcriptome analysis by RNA sequencing revealed that megakaryocytic-related genes were highly expressed. Additional maturation and investigation of hiPSC-derived MKs should provide insights into MK biology and lead to the generation of large numbers of platelets ex vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.