scholarly journals A Review of Advances in Hematopoietic Stem Cell Mobilization and the Potential Role of Notch2 Blockade

2020 ◽  
Vol 29 ◽  
pp. 096368972094714
Author(s):  
Marwah Albakri ◽  
Hammad Tashkandi ◽  
Lan Zhou
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Hematopoietic Stem Cell ◽  
Animal Studies ◽  
Primary Source ◽  
High Yield ◽  
Ligand Interaction ◽  
Hematopoietic Stem ◽  
Cell Mobilization ◽  
Hsc Transplantation

Hematopoietic stem cell (HSC) transplantation can be a potential cure for hematological malignancies and some nonhematologic diseases. Hematopoietic stem and progenitor cells (HSPCs) collected from peripheral blood after mobilization are the primary source to provide HSC transplantation. In most of the cases, mobilization by the cytokine granulocyte colony-stimulating factor with chemotherapy, and in some settings, with the CXC chemokine receptor type 4 antagonist plerixafor, can achieve high yield of hematopoietic progenitor cells (HPCs). However, adequate mobilization is not always successful in a significant portion of donors. Research is going on to find new agents or strategies to increase HSC mobilization. Here, we briefly review the history of HSC transplantation, current mobilization regimens, some of the novel agents that are under investigation for clinical practice, and our recent findings from animal studies regarding Notch and ligand interaction as potential targets for HSPC mobilization.

Bone metabolism markers and angiogenic cytokines as regulators of human hematopoietic stem cell mobilization

2017 ◽  
Vol 36 (4) ◽  
pp. 399-409 ◽  
Author(s):  
Pantelis Tsirkinidis ◽  
Evangelos Terpos ◽  
Georgios Boutsikas ◽  
Athanasios Papatheodorou ◽  
Konstantinos Anargyrou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Bone Metabolism ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Mobilization ◽  
Hematopoietic Stem ◽  
Bone Metabolism Markers ◽  
Hematopoietic Stem Cell Mobilization ◽  
Cell Mobilization ◽  
Angiogenic Cytokines

scholarly journals Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Petter Säwen ◽  
Mohamed Eldeeb ◽  
Eva Erlandsson ◽  
Trine A Kristiansen ◽  
Cecilia Laterza ◽  
...  
Keyword(s):  
Stem Cell ◽  
Steady State ◽  
Progenitor Cells ◽  
Blood Cells ◽  
Lineage Tracing ◽  
Compensatory Mechanism ◽  
Fetal Origins ◽  
Hematopoietic Stem ◽  
Differentiation Capacity ◽  
Hsc Transplantation

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.

scholarly journals Mobilization as a preparative regimen for hematopoietic stem cell transplantation

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3764-3771 ◽  
Author(s):  
Jing Chen ◽  
André Larochelle ◽  
Simon Fricker ◽  
Gary Bridger ◽  
Cynthia E. Dunbar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Donor Cell ◽  
Cxcr4 Antagonist ◽  
Hematopoietic Stem ◽  
Cell Engraftment ◽  
Preparative Regimen ◽  
And Control ◽  
Hsc Transplantation ◽  
Marrow Cells

Current myeloablative conditioning regimens for hematopoietic stem cell (HSC) transplantation are associated with significant morbidity and mortality. Thus, alternative strategies to promote engraftment of infused HSCs with increased safety warrant investigation. Using parabiotic mice, we determined that, after mobilization with AMD3100 (a CXCR4 antagonist), HSCs exited from marrow, transited blood, and engrafted in open niches in partner marrow. We then hypothesized that mobilization before transplantation might vacate niches and improve HSC engraftment. When PeP3b mice were treated with AMD3100 at 2 hours before the transplantation of 4 × 107 marrow cells, donor cell engraftment was higher (4.6% ± 1.1%) than in control animals (no AMD3100; 1.0% ± 0.24%, P < .001). When mice received weekly injections of AMD3100 on 3 consecutive weeks and marrow cells were transplanted 2 hours after each mobilization, donor cell engraftment further increased (9.1% ± 1.7%, P = .001). In contrast, in similar experiments with Balb/cByJ mice that mobilize poorly, there was no difference between the donor cell engraftment of AMD3100-treated and control recipients. These results indicate that the number of available niches regulates the number of HSCs. In addition, mobilization with AMD3100 may provide a safer preparative approach for HSC transplantation in genetic and other nonmalignant disorders.

scholarly journals Lmo2Induces Hematopoietic Stem Cell-Like Features in T-Cell Progenitor Cells Prior to Leukemia

Stem Cells ◽  
2013 ◽  
Vol 31 (5) ◽  
pp. 882-894 ◽  
Author(s):  
Susan M. Cleveland ◽  
Stephen Smith ◽  
Rati Tripathi ◽  
Elizabeth M. Mathias ◽  
Charnise Goodings ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Progenitor Cells ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem

The histone lysine acetyltransferase HBO1 (KAT7) regulates hematopoietic stem cell quiescence and self-renewal

Blood ◽  
2021 ◽  
Author(s):  
Yuqing Yang ◽  
Andrew J Kueh ◽  
Zoe Grant ◽  
Waruni Abeysekera ◽  
Alexandra L Garnham ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Bone Marrow Cells ◽  
High Rate ◽  
Embryonic Patterning ◽  
Self Renewal ◽  
Hematopoietic Stem

The histone acetyltransferase HBO1 (MYST2, KAT7) is indispensable for postgastrulation development, histone H3 lysine 14 acetylation (H3K14Ac) and the expression of embryonic patterning genes. In this study, we report the role of HBO1 in regulating hematopoietic stem cell function in adult hematopoiesis. We used two complementary cre-recombinase transgenes to conditionally delete Hbo1 (Mx1-Cre and Rosa26-CreERT2). Hbo1 null mice became moribund due to hematopoietic failure with pancytopenia in the blood and bone marrow two to six weeks after Hbo1 deletion. Hbo1 deleted bone marrow cells failed to repopulate hemoablated recipients in competitive transplantation experiments. Hbo1 deletion caused a rapid loss of hematopoietic progenitors (HPCs). The numbers of lineage-restricted progenitors for the erythroid, myeloid, B-and T-cell lineages were reduced. Loss of HBO1 resulted in an abnormally high rate of recruitment of quiescent hematopoietic stem cells (HSCs) into the cell cycle. Cycling HSCs produced progenitors at the expense of self-renewal, which led to the exhaustion of the HSC pool. Mechanistically, genes important for HSC functions were downregulated in HSC-enriched cell populations after Hbo1 deletion, including genes essential for HSC quiescence and self-renewal, such as Mpl, Tek(Tie-2), Gfi1b, Egr1, Tal1(Scl), Gata2, Erg, Pbx1, Meis1 and Hox9, as well as genes important for multipotent progenitor cells and lineage-specific progenitor cells, such as Gata1. HBO1 was required for H3K14Ac through the genome and particularly at gene loci required for HSC quiescence and self-renewal. Our data indicate that HBO1 promotes the expression of a transcription factor network essential for HSC maintenance and self-renewal in adult hematopoiesis.

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