Hypoxia and Visualization of the Stem Cell Niche

Dalloul, Ali

doi:10.1007/978-1-62703-508-8_17

Cited by 19 publications

(15 citation statements)

References 29 publications

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“…Hypoxic stem cell niches are routinely detected in various organs by Pimo together with HIF-1α and its downstream targets. 50 It has recently been shown that HSCs with a hypoxic profile are distributed in the bone marrow independently from the proximity to the endosteal surface and adjacency to vascular profiles. 51 …”

Section: Limitationsmentioning

confidence: 99%

c-Kit–Positive Cardiac Stem Cells Nested in Hypoxic Niches Are Activated by Stem Cell Factor Reversing the Aging Myopathy

Sanada¹,

Kim²,

Czarna³

et al. 2014

Circulation Research

106

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Rationale Hypoxia favors stem cell quiescence, while normoxia is required for their activation; but whether cardiac stem cell (CSC) function is regulated by the hypoxic/normoxic state of the cell is currently unknown. Objective A balance between hypoxic and normoxic CSCs may be present in the young heart, although this homeostatic control may be disrupted with aging. Defects in tissue oxygenation occur in the old myocardium, and this phenomenon may expand the pool of hypoxic CSCs, which are no longer involved in myocyte renewal. Methods and Results Here we show that the senescent heart is characterized by an increased number of quiescent CSCs with intact telomeres that cannot reenter the cell cycle and form a differentiated progeny. Conversely, myocyte replacement is controlled only by frequently dividing CSCs with shortened telomeres; these CSCs generate a myocyte population that is chronologically young but phenotypically old. Telomere dysfunction dictates their actual age and mechanical behavior. However, the residual subset of quiescent young CSCs can be stimulated in situ by stem cell factor reversing the aging myopathy. Conclusions Our findings support the notion that strategies targeting CSC activation and growth interfere with the manifestations of myocardial aging in an animal model. Although caution has to be exercised in the translation of animal studies to human beings, our data strongly suggests that a pool of functionally-competent CSCs persists in the senescent heart and this stem cell compartment can promote myocyte regeneration effectively, correcting partly the aging myopathy.

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Section: Limitationsmentioning

confidence: 99%

c-Kit–Positive Cardiac Stem Cells Nested in Hypoxic Niches Are Activated by Stem Cell Factor Reversing the Aging Myopathy

Sanada¹,

Kim²,

Czarna³

et al. 2014

Circulation Research

106

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“…Stem cell niches are proposed as physical and dynamic spaces that transmit and receive signals to govern stem cell quiescence and self-renewal [45]. This local microenvironment also protects stem cells by maintaining a low partial oxygen pressure [46]. Indeed, it has been described that hypoxia-inducible factors regulate the HSC niche [47].…”

Section: Diversity Of the Stem Cell Nichementioning

confidence: 99%

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

Pérez

Lucas

Gálvez

2018

Cell Physiol Biochem

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The stem cell field has grown very rapidly during the last decade, offering the promise of innovative therapies to treat disease. Different stem cell populations have been isolated from various human adult tissues, mainly from bone marrow and adipose tissue, but many other body tissues harbor a stem cell population. Adult tissue stem cells are invariably found in discrete microenvironments termed niches, where they play key roles in tissue homeostasis by enabling lifelong optimization of organ form and function. Some diseases are known to strike at the stem cell population, through alterations in their specific microenvironments, making them non-viable. Furthermore, it has been shown that a transformed stem cell population could prompt the development of certain cancers. This review focuses on the potential negative aspects of a range of diseases on the activity of stem cells and how their potential use in cell therapies may be affected.

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“…It has been reported that increased ROS levels can inhibit HSC self-renewal pathways such as Wnt-b-catenin (Undi et al, 2016;Shin et al, 2004), and activate pathways that may lead to self-renewal defects such as p38 MAPK, mTOR, and more (Ito et al, 2004;Ito et al, 2006;Yoshida et al, 2011). In fact, primitive HSCs exist in a low-oxygen niche that restricts ROS production and provides long-term protection for cells (Jang and Sharkis, 2007;Dalloul, 2013). However, some researches have proved that HSCs cultured in vitro, together with the commonly used hydrophobic materials such as polystyrene dishes or flasks, could produce excessive level of ROS, which is a well-known cause of HSC differentiation (Bigarella et al, 2014;Yu et al, 2015;Cao et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells

Zhang

et al. 2020

Front. Pharmacol.

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There is an increasing demand for the expansion of functional human hematopoietic stem cells (hHSCs) for various clinical applications. Based on our primary screening of antioxidant small molecule compounds library, a small molecule compound C2968 (chrysin) was identificated to expand cord blood CD34 + cells in vitro. Then we further verified the optimum concentration and explored its effect on hHSCs phenotype and biological function. C2968 could significantly increase the proportion and absolute number of CD34 + CD38 − CD49f + and CD34 + CD38 − CD45RA − CD90 + cells under 2.5 mM. Furthermore, the total number of colony-forming units and the frequency of LT-HSCs in C2968-treated group were significantly higher than control, indicating the multipotency and long-term activity of hematopoietic stem and progenitor cells were sustained. Additionally, C2968 treatment could maintain transplantable HSCs that preserve balanced multilineage potential and promote rapid engraftment after transplantation in immunodeficient (NOG) mice. Mechanistically, the activity of chrysin might be mediated through multiple mechanisms namely delaying HSC differentiation, inhibiting ROS-activated apoptosis, and modulating of cyclin-dependent kinase inhibitors. Overall, chrysin showed good ex vivo expansion effect on hHSCs, which could maintain the self-renewal and multilineage differentiation potential of hHSCs. Through further research on its antioxidant mechanism, it may become a promising tool for further fundamental research and clinical umbilical cord blood transplantation of hHSCs.

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Hypoxia and Visualization of the Stem Cell Niche

Cited by 19 publications

References 29 publications

c-Kit–Positive Cardiac Stem Cells Nested in Hypoxic Niches Are Activated by Stem Cell Factor Reversing the Aging Myopathy

c-Kit–Positive Cardiac Stem Cells Nested in Hypoxic Niches Are Activated by Stem Cell Factor Reversing the Aging Myopathy

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells

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