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A causal link between hematopoietic stem/progenitor cell (HSPC) dysfunction and DNA damage accrual has been proposed. Clinically relevant strategies to maintain genome integrity in these cells are needed. Here we report that eltrombopag, a small molecule agonist of the thrombopoietin (TPO) receptor used in the clinic, promotes DNA double strand break (DSB) repair in human HSPCs. We demonstrate that eltrombopag specifically activates the classical non-homologous end joining (C-NHEJ) DNA repair mechanism, a pathway known to support genome integrity. Eltrombopag-mediated DNA repair results in enhanced genome stability, survival and function of primary human HSPCs, as demonstrated in karyotyping analyses, colony forming unit assays and after transplantation in immunodeficient NSG mice. Eltrombopag may offer a new therapeutic modality to protect human HSPCs against genome insults.
This article was published in the following journal.
Name: Experimental hematology
We used RNA-sequencing (RNA-Seq) technology and an old hematopoietic stem and progenitor cells (HSPCs) model in vitro to analyze differential expressions of mismatch repair (MMR)-related genes in aged...
Inflammatory cells in atherosclerotic plaque exclusively originate from hematopoietic stem/progenitor cells (HSPCs). In this study, we investigated whether circulating HSPCs frequency related to coron...
Bmi-1 gene is well recognized as an oncogene, but has been recently demonstrated to play a role in the self-renewal of tissue-specific stem cells. By using Bmi-1 mice, we investigated the role of Bmi-...
Refractory thrombocytopenia is a frequent and severe complication after haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) and lacks effective treatment strategies. Eltromb...
This study evaluates the addition of Eltrombopag after Hematopoietic stem cell transplantation (HSCT) to improve the engraftment of hematopoietic stem cell. Half of the participants will r...
This is a phase I/II study evaluating safety and efficacy of autologous hematopoietic stem and progenitor cells genetically modified with IDUA lentiviral vector encoding for the human α-L...
There is currently no standard treatment for patients with neuro-epithelial (brain) or other solid tumors in another part of the body who do not have adequate suitable autologous hematopoi...
The purpose of this phase II open-label, single-arm 36-week clinical trial is to evaluate the effect of eltrombopag in patients with poor graft function (PGF) after allogeneic-hematopoieti...
The purpose of this study is to evaluate the safety and the efficacy of Human T Lymphoid Progenitor (HTLP) injection to accelerate immune reconstitution after partially HLA compatible allo...
Stem cells derived from HEMATOPOIETIC STEM CELLS. Derived from these myeloid progenitor cells are the MEGAKARYOCYTES; ERYTHROID CELLS; MYELOID CELLS; and some DENDRITIC CELLS.
Progenitor cells from which all blood cells derive.
Specialized stem cells that are committed to give rise to cells that have a particular function; examples are MYOBLASTS; MYELOID PROGENITOR CELLS; and skin stem cells. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from: http://www.nih.gov/news/stemcell/primer.htm)
Bipotential angio-hematopoietic stem cells that give rise to both HEMATOPOIETIC STEM CELLS and ENDOTHELIAL CELLS.
The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...