Stem cell technology

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

Targeted Gene Modification of Hematopoietic Progenitor Cells in Mice Following Systemic Administration of a PNA-peptide Conjugate

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

PI3-Kinase Deletion Dysregulates Autophagy in HSCs and Promotes Myelodysplasia

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

The Protean Nature of Cells in the B Lymphocyte Lineage

Reduced Erg Dosage Perturbs Fetal and Adult Hematopoiesis

Journal of HematotherapyVol. 7, No. 2 Not All Healthy Donors Mobilize Hematopoietic Progenitor Cells Sufficiently After G-CSF Administration to Allow for Subsequent CD34 Purification of the Leukapheresis ProductMette Holm and Peter HoklandMette HolmSearch for more papers by this author and Peter HoklandSearch for more papers by this authorPublished Online:27 Mar 2009https://doi.org/10.1089/scd.1.1998.7.111AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byCollecting and Processing of the GraftPBSCs Sphingoling along S1P/S1P1 axisBlood, Vol. 119, No. 3The Plasminogen System in Regulating Stem Cell MobilizationJournal of Biomedicine and Biotechnology, Vol. 2012Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics10 November 2011 | Transfusion, Vol. 51Plasminogen Regulates Stromal Cell–Derived Factor-1/CXCR4–Mediated Hematopoietic Stem Cell Mobilization by Activation of Matrix Metalloproteinase-9Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 31, No. 9Enhancement of the efficacy of therapeutic proteins by formulation with PEGylated liposomes; a case of FVIII, FVIIa and G-CSF24 January 2010 | Expert Opinion on Drug Delivery, Vol. 7, No. 2Mobilization of Hematopoietic Cells Prior to Autologous or Allogeneic Transplantation27 November 2009Binding of proteins to PEGylated liposomes and improvement of G-CSF efficacy in mobilization of hematopoietic stem cellsJournal of Controlled Release, Vol. 135, No. 1Peripheral blood stem cell mobilization: new regimens, new cells, where do we standCurrent Opinion in Hematology, Vol. 15, No. 4Granulocyte Colony-Stimulating Factor Increases Hepatic Sinusoidal Perfusion During Liver Regeneration in Mice9 July 2009 | Journal of Investigative Surgery, Vol. 21, No. 2Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF?19 March 2007 | Bone Marrow Transplantation, Vol. 39, No. 10Rapid succession of peripheral blood progenitor cell mobilization cycles in patients with chronic heart failure: effects on the hematopoietic systemTransfusion, Vol. 46, No. 8Circulating Hematopoietic Stem Cell TransplantationNeutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GROβ/CXCL2 and GROβT /CXCL2Δ4Blood, Vol. 103, No. 1It's moving day: factors affecting peripheral blood stem mobilization and strategies for improvement23 July 2003 | British Journal of Haematology, Vol. 122, No. 3The whys and hows of hematopoietic progenitor and stem cell mobilization12 March 2003 | Bone Marrow Transplantation, Vol. 31, No. 5Plasma from poorly mobilizing human subjects inhibits cytokine-induced murine blood stem-cell mobilizationCytotherapy, Vol. 4, No. 4GM-CSF-based mobilization effect in normal healthy donors for allogeneic peripheral blood stem cell transplantation22 July 2002 | Bone Marrow Transplantation, Vol. 30, No. 2Analysis of factors associated with low peripheral blood progenitor cell collection in normal donorsTransfusion, Vol. 42, No. 1Donor age-related differences in PBPC mobilization with rHuG-CSFTransfusion, Vol. 41, No. 2Stem Cell Collection for Hematopoietic Transplantation: Stem Cell Sources, Mobilization Strategies, and Factors that Influence YieldMobilization of blood-derived stem and progenitor cells in normal subjects by granulocyte-macrophage- and granulocyte-colony-stimulating factors19 December 2002 | Transfusion, Vol. 39, No. 1 Volume 7Issue 2Apr 1998 To cite this article:Mette Holm and Peter Hokland.Not All Healthy Donors Mobilize Hematopoietic Progenitor Cells Sufficiently After G-CSF Administration to Allow for Subsequent CD34 Purification of the Leukapheresis Product.Journal of Hematotherapy.Apr 1998.111-113.http://doi.org/10.1089/scd.1.1998.7.111Published in Volume: 7 Issue 2: March 27, 2009PDF download

Human Thrombopoietin Knockin Mice Efficiently Support Human Hematopoiesis In Vivo

Recent evidence suggests that the environment-sensing transcription factor aryl hydrocarbon receptor (AHR) is an important regulator of hematopoiesis. Yet, the mechanisms and extent of AHR-mediated regulation within the most primitive hematopoietic cells, hematopoietic stem and progenitor cells (HSPCs), are poorly understood. Through a combination of transcriptomic and flow cytometric approaches, this study provides new insight into how the AHR influences hematopoietic stem and progenitor cells. Comparative analysis of intraphenotypic transcriptomes of hematopoietic stem cells (HSCs) and multipotent progenitor (MPP) cells from AHR knockout (AHR KO) and wild type mice revealed significant differences in gene expression patterns. Notable among these were differences in expression of cell cycle regulators, specifically an enrichment of G2/M checkpoint genes when Ahr was absent. This included the regulator Aurora A kinase (Aurka, AurA). Analysis of AurA protein levels in HSPC subsets using flow cytometry, in combination with inducible AHR KO or in vivo AHR antagonism, showed that attenuation of AHR increased levels of AurA in HSCs and lineage-biased MPP cells. Overall, these data highlight a potential novel mechanism by which AHR controls HSC homeostasis and HSPC differentiation. These findings advance the understanding of how AHR influences and regulates primitive hematopoiesis.

Introduction: Myelodysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia (CMML) are clonal disorders driven by progressively acquired somatic mutations in hematopoietic stem cells (HSC) and characterized by the accumulation of blasts in the bone marrow and accompanying cytopenias. Hypomethylating agents (HMA) such as azacytidine (AZA) can modify the clinical course of MDS and CMML (Platzbecker et al Blood 2019). Although not curative, they are used as first-line therapies for high-risk patients who are ineligible or unable to access an allogeneic bone marrow transplant. Clinical improvement in response to HMAs is not accompanied by clearance or major shifts in mutant clones in the bone marrow (Unnikrishnan et al Cell Reports 2017, Merlevede et al Nature Communications 2016). However, it is unclear whether in patients with established MDS; (a) hematopoietic stem and progenitor cells with multiple mutations progress through to mature cells with comparable robustness to their counterparts with fewer or no mutations, or (b) the improvements in peripheral blood counts following HMA therapy is driven by residual wild-type hematopoietic stem and progenitor cells or by clones with particular combinations of mutations. Methods: We index sorted hematopoietic stem (HSC, MPP) and progenitor cells (CMP, MEP and GMP) and mature blood cells (neutrophils (Neut), monocytes (Mono), and naïve B-cells (nBC): short lived cell types representative of current stem/progenitor output) from 3 MDS/CMML patients (1 treatment naïve, 2 treated >10 years with AZA) and performed targeted amplicon sequencing on thousands of single cells (n = 4248). In a second cohort (9 MDS patients; 6 responders, 3 non-responders) we sorted Mono, natural killer (NK) cells, and CD33+ progenitors and measured variant allele fraction (VAF) before and after 6 cycles of AZA. Results: Single cell data showed the proportion of residual wild-type HSCs, and their contribution to mature myeloid cells, was minor (0 - 5.3% of HSCs, 0.3 - 4.5% of mature myeloid cells). Driver mutations were proportionately represented across multiple hematopoietic cell types, and even the most mutated stem and progenitor clones maintained their capacity to differentiate to mature myeloid and, in some cases, lymphoid cell types in vivo, irrespective of AZA treatment (Fig A). In a second cohort composed of paired pre- and post-AZA samples, clonal composition differed slightly between cell types; e.g. NK cells often harbored lower VAFs compared to monocytes and progenitors. We also observed treatment-associated reduction in a minority of mutated clones in this cohort. However, in all patients, clonal composition was remarkably similar before and after treatment, with highly mutated progenitors making a significant contribution to mature cells, even in patients showing reduced blast plus improved blood counts (Fig B). Conclusions: Highly mutated immature cells contribute significantly to mature blood production in MDS and CMML, before and after AZA treatment. Our data highlight the key role of AZA therapy to promote output from mutant progenitors rather than simply eradicating them. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A vast literature exists on the biology of blood formation and regeneration under experimental and clinical conditions. The field of hematopoiesis was recently advanced by the capacity to purify to homogeneity primitive hematopoietic stem and progenitor cells. Isolation of cells at defined maturational stages has enhanced the understanding of the fundamental nature of stem cells, including how cell fate decisions are made, and this understanding is relevant to the development of other normal as well as malignant tissues. This review updates the basic biology of hematopoietic stem cells (HSC) and progenitors, the evolving use of purified HSC as grafts for clinical hematopoietic cell transplantation (HCT) including immune tolerance induction, and the application of HSC biology to other stem cell fields.

EGFP Is a Useful Long-Term Expression Tracer for Hematopoietic Stem Cells While DsRed Fluorescent Protein Is Not.