ArticleStem cells and development2011
Inhibition of p38 mitogen-activated protein kinase promotes ex vivo hematopoietic stem cell expansion.
Article in Stem cells and development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Hematopoietic (stem) cells-The elixir of life?FEBS letters · 2026Review
- Low Dose Methotrexate Has Divergent Effects on Cycling and Resting Human Hematopoietic Stem and Progenitor Cells.Clinical and translational science · 2025Article
- Emerging roles of mitochondrial functions and epigenetic changes in the modulation of stem cell fate.Cellular and molecular life sciences : CMLS · 2024Review
- Review
- Effects of signaling pathway inhibitors on hematopoietic stem cells.Molecular medicine reports · 2021Article
- Coinhibition of activated p38 MAPKα and mTORC1 potentiates stemness maintenance of HSCs from SR1-expanded human cord blood CD34Stem cells translational medicine · 2020Article
- Competitive sgRNA Screen Identifies p38 MAPK as a Druggable Target to Improve HSPC Engraftment.Cells · 2020Article
- Regulation of Hematopoietic Stem Cell Fate and Malignancy.International journal of molecular sciences · 2020Review
- An Acromegaly Disease Zebrafish Model Reveals Decline in Body Stem Cell Number along with Signs of Premature Aging.Biology · 2020Article
- Network Pharmacology-Based Investigation of the System-Level Molecular Mechanisms of the Hematopoietic Activity of Samul-Tang, a Traditional Korean Herbal Formula.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Sitagliptin Mitigates Total Body Irradiation-Induced Hematopoietic Injury in Mice.Oxidative medicine and cellular longevity · 2020Article
- In Vitro Expansion of Hematopoietic Stem Cells by Inhibition of Both GSK3 and p38 Signaling.Stem cells and development · 2019Article
- Expansion of primitive human hematopoietic stem cells by culture in a zwitterionic hydrogel.Nature medicine · 2019Article
- Ex Vivo Expansion of CD34Stem cells translational medicine · 2018Article
- Article
- Loss of DEK induces radioresistance of murine restricted hematopoietic progenitors.Experimental hematology · 2018Article
- Molecular and epigenetic regulatory mechanisms of normal stem cell radiosensitivity.Cell death discovery · 2018Review
- Juglanin inhibits lung cancer by regulation of apoptosis, ROS and autophagy induction.Oncotarget · 2017Article
- Angelica sinensis Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil.International journal of molecular sciences · 2017Article
- Preventing aging with stem cell rejuvenation: Feasible or infeasible?World journal of stem cells · 2017Article
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Hematopoietic stem cell (HSC) self-renewal is tightly regulated by a complex crosstalk between many cell-intrinsic regulators and a variety of extrinsic signals from the stem cell niche. In this study, we examined whether the p38 mitogen-activated protein kinase (p38) is one of the intrinsic regulators that can negatively regulate HSC self-renewal in vitro and whether inhibition of p38 activity with a small molecule inhibitor can promote HSC expansion ex vivo. The results from this study showed that sorted mouse bone marrow Lin(-)Sca1(+)c-kit(+) cells (LSK(+) cells) exhibited selective activation of p38 after culture in a serum-free medium supplemented with 100 ng/mL stem cell factor, thrombopoietin, and Flt3 ligand. The activation of p38 was associated with a significant reduction in HSCs and induction of apoptosis and cellular senescence in LSK(+) cells and their progeny. Addition of the specific p38 inhibitor SB203580 (SB, 5 μM) to the culture inhibited the activation of p38 in LSK(+) cells, which led to increase in HSC self-renewal and ex vivo expansion as shown by the cobblestone area forming cell assay, competitive repopulation, and serial transplantation. The increase in HSC expansion is likely attributable to SB-mediated inhibition of HSC apoptosis and senescence and upregulation of HoxB4 and CXCR4. These findings suggest that p38 plays an important role in the regulation of HSC self-renewal in vitro and inhibition of p38 activation with a small molecule inhibitor may represent a novel approach to promote ex vivo expansion of HSCs.
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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.