Unlocking hematopoietic stem cell potential: integrative computational approaches for genomic and transcriptomic analysis

Are transplantable stem cells required for adult hematopoiesis?

Quiescence regulators for hematopoietic stem cell

Stem cell gene transfer—efficacy and safety in large animal studies

Stem cell technology is a rapidly developing field that combines the efforts of cell biologists, geneticists, and clinicians and offers hope of effective treatment for a variety of malignant and...

Human Hematopoietic Stem Cells Have Altered Mitochondrial Activity after Stem Cell Transplantation

A non-telomeric role of POT1a in regulating HSC metabolism via TIN2 localization

Ex Vivo Expanded Hematopoietic Stem Cells Overcome the MHC Barrier in Allogeneic Transplantation

The Protean Nature of Cells in the B Lymphocyte Lineage

PI3-Kinase Deletion Dysregulates Autophagy in HSCs and Promotes Myelodysplasia

Sickle cell disease is characterized by chronic anemia and vaso-occlusive crises, which eventually lead to multi-organ damage and premature death. Hematopoietic stem cell transplantation is the only curative treatment but it is limited by toxicity and poor availability of HLA-compatible donors. A gene therapy approach based on the autologous transplantation of lentiviral-corrected hematopoietic stem and progenitor cells was shown to be efficacious in one patient. However, alterations of the bone marrow environment and properties of the red blood cells hamper the harvesting and immunoselection of patients’ stem cells from bone marrow. The use of Filgrastim to mobilize large numbers of hematopoietic stem and progenitor cells into the circulation has been associated with severe adverse events in sickle cell patients. Thus, broader application of the gene therapy approach requires the development of alternative mobilization methods. We set up a phase I/II clinical trial whose primary objective was to assess the safety of a single injection of Plerixafor in sickle cell patients undergoing red blood cell exchange to decrease the hemoglobin S level to below 30%. The secondary objective was to measure the efficiency of mobilization and isolation of hematopoietic stem and progenitor cells. No adverse events were observed. Large numbers of CD34+ cells were mobilized extremely quickly. Importantly, the mobilized cells contained high numbers of hematopoietic stem cells, expressed high levels of stemness genes, and engrafted very efficiently in immunodeficient mice. Thus, Plerixafor can be safely used to mobilize hematopoietic stem cells in sickle cell patients; this finding opens up new avenues for treatment approaches based on gene addition and genome editing. Clinicaltrials.gov identifier: NCT02212535.

Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells Using a Natural Product, Garcinol

Foxo3-Mediated Redox Regulation Is Required for DNA Damage Response in Hematopoietic Stem Cells.

Data Driven Computational Modeling of Hematopoiesis in Myelodysplastic Syndromes Unveils Differences in Hematopoietic Stem Cell Kinetics Compared to Age-Matched Healthy Controls

Interferon-Gamma Impairs Expansion and Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells

A Conserved Cis-Regulatory Retinoic Acid Responsive Element Is Essential for Maintenance of Primitive Hematopoietic Stem Cells through Regulation of Hoxb Cluster