The biology of hematopoietic stem cells and its clinical implications

Skulimowska, Izabella; Sośniak, Justyna; Gonka, Monika; Szade, Agata; Józkowicz, Alicja; Szade, Krzysztof

doi:10.1111/febs.16192

Cited by 12 publications

(6 citation statements)

References 144 publications

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“…Each of these defined fractions preferentially differentiates toward selected lineage probably due to the transcriptional lineage priming ( 26 ). Nonetheless, the hierarchical relationship between the balanced and lineage-biased fractions within the HSC pool still remains not fully understood ( 27 ). The differences are also evident between HSCs from young and old individuals.…”

Section: The Phenomenon Of Blood Productionmentioning

confidence: 99%

“…The differences are also evident between HSCs from young and old individuals. Aged HSCs show limited self-renewal, lower regenerative potential and increased lineage-biased differentiation upon transplantation ( 22 , 23 , 27 , 28 ).…”

Section: The Phenomenon Of Blood Productionmentioning

confidence: 99%

“…But up to date, there are no markers specific for preleukemic HSCs ( 126 ). Nevertheless, some studies on mouse models propose a few markers to categorize a heterogenic pool of strictly defined murine HSCs ( 27 ). We and others showed that it is possible to prospectively isolate minor fractions of lineage-biased HSCs ( 23 ).…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

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The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

Filipek-Gorzała,

Kwiecińska,

Szade

et al. 2024

Front. Oncol.

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Hematopoietic stem cells (HSCs) produce all blood cells throughout the life of the organism. However, the high self-renewal and longevity of HSCs predispose them to accumulate mutations. The acquired mutations drive preleukemic clonal hematopoiesis, which is frequent among elderly people. The preleukemic state, although often asymptomatic, increases the risk of blood cancers. Nevertheless, the direct role of preleukemic HSCs is well-evidenced in adult myeloid leukemia (AML), while their contribution to other hematopoietic malignancies remains less understood. Here, we review the evidence supporting the role of preleukemic HSCs in different types of blood cancers, as well as present the alternative models of malignant evolution. Finally, we discuss the clinical importance of preleukemic HSCs in choosing the therapeutic strategies and provide the perspective on further studies on biology of preleukemic HSCs.

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Section: The Phenomenon Of Blood Productionmentioning

confidence: 99%

Section: The Phenomenon Of Blood Productionmentioning

confidence: 99%

Section: Perspectives and Conclusionmentioning

confidence: 99%

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The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

Filipek-Gorzała,

Kwiecińska,

Szade

et al. 2024

Front. Oncol.

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“…The multipotent progenitor pool of HSCs is heterogeneous and can be divided into long-term repopulating HSCs (LT-HSCs), short-term HSCs (ST-HSCs), and multipotent progenitors (MPPs) populations ( 1 ). LT-HSCs have a long-lasting capacity of self-renewal and differentiation, enable lifelong production of all hematopoietic lineages, and the replenish the hematopoietic system after injury or transplantation ( 2 ). ST-HSCs and MPPs that are differentiated from LT-HSCs have rapid proliferation and wide differentiation potential, but ST-HSCs have just a transient self-renewal ability and do not possess the same long-term self-renewal capacity as LT-HSCs ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

The maintenance mechanism of hematopoietic stem cell dormancy: role for a subset of macrophages

Kwon

Kim

Chae

et al. 2023

BMB Rep

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Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.

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“…Aging of the BM micro-environment also favors disease progression. Age-related alterations involve the increased frequency of myeloid cells parallel to a decline of lymphopoiesis, red cell abnormalities like anemia, and a higher incidence of myeloid disorders, like myeloid dysplastic syndrome and acute myeloid leukemia ( Pang et al, 2011 ; Skulimowska et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Functionalized 3D scaffolds for engineering the hematopoietic niche

Bruschi

Vanzolini

Sahu

et al. 2022

Front. Bioeng. Biotechnol.

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Hematopoietic stem cells (HSCs) reside in a subzone of the bone marrow (BM) defined as the hematopoietic niche where, via the interplay of differentiation and self-renewal, they can give rise to immune and blood cells. Artificial hematopoietic niches were firstly developed in 2D in vitro cultures but the limited expansion potential and stemness maintenance induced the optimization of these systems to avoid the total loss of the natural tissue complexity. The next steps were adopted by engineering different materials such as hydrogels, fibrous structures with natural or synthetic polymers, ceramics, etc. to produce a 3D substrate better resembling that of BM. Cytokines, soluble factors, adhesion molecules, extracellular matrix (ECM) components, and the secretome of other niche-resident cells play a fundamental role in controlling and regulating HSC commitment. To provide biochemical cues, co-cultures, and feeder-layers, as well as natural or synthetic molecules were utilized. This review gathers key elements employed for the functionalization of a 3D scaffold that demonstrated to promote HSC growth and differentiation ranging from 1) biophysical cues, i.e., material, topography, stiffness, oxygen tension, and fluid shear stress to 2) biochemical hints favored by the presence of ECM elements, feeder cell layers, and redox scavengers. Particular focus is given to the 3D systems to recreate megakaryocyte products, to be applied for blood cell production, whereas HSC clinical application in such 3D constructs was limited so far to BM diseases testing.

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The biology of hematopoietic stem cells and its clinical implications

Cited by 12 publications

References 144 publications

The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

The maintenance mechanism of hematopoietic stem cell dormancy: role for a subset of macrophages

Functionalized 3D scaffolds for engineering the hematopoietic niche

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