ArticleThe Journal of clinical investigation2015
Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- Endothelial cell heterogeneity drives angiogenesis in endometriosis: mechanisms and emerging organoid-based models.Apoptosis : an international journal on programmed cell death · 2026Review
- Unleashing innovative cross-organ fibrosis therapies by harnessing the omics revolution.JCI insight · 2026Review
- Preclinical efficacy of tasquinimod in myelodysplastic neoplasms: Restoring erythropoiesis and mitigating bone loss.HemaSphere · 2026Article
- Biomimetic Nanoparticles for Bone Regeneration: Construction Strategies and Therapeutic Mechanisms.International journal of nanomedicine · 2026Review
- Architectural Design of Biomaterial Scaffolds for Hematopoietic Stem Cell Culture.Biomaterials research · 2025Review
- A genetically inducible endothelial niche enables vascularization of human kidney organoids with multilineage maturation and emergence of renin expressing cells.Kidney international · 2024Article
- Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative.Stem cell research & therapy · 2024Article
- Application of extracellular vesicles in diabetic osteoporosis.Frontiers in endocrinology · 2024Review
- Article
- Genetically engineering endothelial niche in human kidney organoids enables multilineage maturation, vascularization and de novo cell types.bioRxiv : the preprint server for biology · 2023Article
- De Novo Generation of Human Hematopoietic Stem Cells from Pluripotent Stem Cells for Cellular Therapy.Cells · 2023Review
- Endothelial and hematopoietic hPSCs differentiation via a hematoendothelial progenitor.Stem cell research & therapy · 2022Article
- Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds.Bioactive materials · 2021Review
- Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions.International journal of molecular sciences · 2021Review
- Single-cell transcriptome of early hematopoiesis guides arterial endothelial-enhanced functional T cell generation from human PSCs.Science advances · 2021Article
- Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing.International journal of molecular sciences · 2021Review
- Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential.NPJ Regenerative medicine · 2021Review
- Comparative engraftment and clonality of macaque HSPCs expanded on human umbilical vein endothelial cells versus non-expanded cells.Molecular therapy. Methods & clinical development · 2021Article
- Biomechanical Regulation of Hematopoietic Stem Cells in the Developing Embryo.Current tissue microenvironment reports · 2021Article
- Hematopoietic stem cells from pluripotent stem cells: Clinical potential, challenges, and future perspectives.Stem cells translational medicine · 2020Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
Abstract
Pluripotent stem cells (PSCs) represent an alternative hematopoietic stem cell (HSC) source for treating hematopoietic disease. The limited engraftment of human PSC-derived (hPSC-derived) multipotent progenitor cells (MPP) has hampered the clinical application of these cells and suggests that MPP require additional cues for definitive hematopoiesis. We hypothesized that the presence of a vascular niche that produces Notch ligands jagged-1 (JAG1) and delta-like ligand-4 (DLL4) drives definitive hematopoiesis. We differentiated hes2 human embryonic stem cells (hESC) and Macaca nemestrina-induced PSC (iPSC) line-7 with cytokines in the presence or absence of endothelial cells (ECs) that express JAG1 and DLL4. Cells cocultured with ECs generated substantially more CD34+CD45+ hematopoietic progenitors compared with cells cocultured without ECs or with ECs lacking JAG1 or DLL4. EC-induced cells exhibited Notch activation and expressed HSC-specific Notch targets RUNX1 and GATA2. EC-induced PSC-MPP engrafted at a markedly higher level in NOD/SCID/IL-2 receptor γ chain-null (NSG) mice compared with cytokine-induced cells, and low-dose chemotherapy-based selection further increased engraftment. Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction were similar to levels achieved for cord blood-derived MPP and up to 20-fold higher than those achieved with hPSC-derived MPP engraftment. Our findings indicate that endothelial Notch ligands promote PSC-definitive hematopoiesis and production of long-term engrafting CD34+ cells, suggesting these ligands are critical for HSC emergence.
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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.