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Hematopoietic System under Physiological Conditions and Following Hematopoietic Reconstitution or Stress: 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 December 2024 | Viewed by 1787

Special Issue Editor


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Guest Editor
Laboratory of Stem and Progenitor Cell Biology, Engelhardt Institute of Molecular Biology RAS, Vavilov Str. 32, 119991 Moscow, Russia
Interests: clonal hematopoiesis, cardiovascular diseases and hematopoietic stem cells
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Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue entitled Hematopoietic System under Physiological Conditions and Following Hematopoietic Reconstitution or Stress.

The seminal work of Till & McCulloch on CFU-Ss in 1961 proved the remarkable conjecture of Maximov some 50 years earlier on the existence of hematopoietic stem cells (HSCs) and laid foundations for their quantitative analysis. Ever since then, in this field, leading labs have dedicated significant effort to the progressive refinement of HSC features and physical isolation of more defined HSC and progenitor cell populations. This was mainly achieved with the use of monoclonal antibodies developed against various blood cell subsets, whereas transplantation into irradiated hosts has been accepted as a gold standard for quantitative functional characterization of purified cell fractions.

These efforts resulted in the appearance of a hierarchical, pyramidal model of blood cell differentiation, which presented a clear-cut scheme of stages that HCSs follow to produce huge amounts of differentiated blood cells to meet the physiological needs of an organism. The hierarchical model provided a very rational and logical explanation of how the hematopoietic system works. Alas, nature rarely follows human reasoning, and this model has not become an exception. The recent introduction of new sophisticated techniques such as single-cell transplantation, specific cell lineage/stage marking using transgenic mouse lines, cell barcoding, next-generation sequencing, single-cell transcriptome analysis, and related bioinformatics tools demonstrated that patterns of HSC differentiation are likely more complex than previously thought. Moreover, recent studies demonstrate that hematopoiesis established in irradiated animals using transplanted cell fractions, and the physiological steady-state hematopoiesis taking place in non-treated animals, not only formally differ from each other, but represent fairly different physiological systems, in which the same cell subsets may demonstrate contrasting behaviors. Given the currently accepted notion that the behavior of HSCs is determined to a large extent by the niches in which they reside, this difference may be partly explained by the irradiation damage sustained by the niche components and, possibly, peculiarities of homing to niches of various cell subsets in different physiological states. As suggested by some recent indirect data, it cannot be taken for granted that HSCs detached from their niches and subjected to significant stress during cell sorting do not substantially change their properties. If such a change occurs, this may warrant a significant revision of the results of previous experiments with transplanted sorted cells.

The true size of the “iceberg” of the complexity of the hematopoietic system is just becoming apparent and, obviously, many more studies using the most advanced techniques are needed to obtain accurate and consistent knowledge of how the hematopoietic system work. In this Special Issue, we invite researchers to submit original research articles on HSC/progenitor cells, hematopoietic microenvironment, and hematopoiesis under different conditions, or reviews on the last developments in these fields.

Dr. Alexander V. Belyavsky
Guest Editor

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Keywords

  • hematopoietic stem/progenitor cells
  • hematopoietic differentiation
  • hematopoietic niches
  • niche-HSC/progenitor cell interactions
  • steady-state hematopoiesis
  • reconstituted hematopoiesis
  • hematopoietic stress response
  • cell fate tracing

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Published Papers (1 paper)

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Research

13 pages, 2313 KiB  
Article
Lentivirus-Mediated BCL-XL Overexpression Inhibits Stem Cell Apoptosis during Ex Vivo Expansion and Provides Competitive Advantage Following Xenotransplantation
by Patricia M. A. Zehnle, Ying Wu, Naile Koleci, Sheila Bohler and Miriam Erlacher
Int. J. Mol. Sci. 2024, 25(7), 4105; https://doi.org/10.3390/ijms25074105 - 7 Apr 2024
Viewed by 1113
Abstract
Hematopoietic reconstitution after hematopoietic stem cell transplantation (HSCT) is influenced by the number of transplanted cells. However, under certain conditions donor cell counts are limited and impair clinical outcome. Hematopoietic stem and progenitor cell (HSPC) expansion prior to HSCT is a widely used [...] Read more.
Hematopoietic reconstitution after hematopoietic stem cell transplantation (HSCT) is influenced by the number of transplanted cells. However, under certain conditions donor cell counts are limited and impair clinical outcome. Hematopoietic stem and progenitor cell (HSPC) expansion prior to HSCT is a widely used method to achieve higher donor cell counts and minimize transplantation-related risks such as graft failure or delayed engraftment. Still, expansion in a non-physiological environment can trigger cell death mechanisms and hence counteract the desired effect. We have shown earlier that during HSCT a relevant amount of HSPCs were lost due to apoptosis and that cell death inhibition in donor HSPCs improved engraftment in xenotransplantation experiments. Here, we assessed the effect of combined ex vivo expansion and cell death inhibition on HSPC yield and their reconstitution potential in vivo. During expansion with cytokines and the small molecule inhibitor StemRegenin 1, concomitant lentiviral overexpression of antiapoptotic BCL-XL resulted in an increased yield of transduced HSPCs. Importantly, BCL-XL overexpression enhanced the reconstitution potential of HSPCs in xenotransplantation experiments in vivo. In contrast, treatment with caspase and necroptosis inhibitors had no favorable effects on HSPC yields nor on cell viability. We postulate that overexpression of antiapoptotic BCL-XL, both during ex vivo expansion and transplantation, is a promising approach to improve the outcome of HSCT in situations with limited donor cell numbers. However, such apoptosis inhibition needs to be transient to avoid long-term sequelae like leukemia. Full article
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