Reactive Oxygen Species Limit the Ability of Bone Marrow Stromal Cells to Support Hematopoietic Reconstitution in Aging Mice

Khatri, Rahul; KrishnanShyam,; RoySushmita,; ChattopadhyaySaborni,; KumarVikash,; MukhopadhyayAsok,

doi:10.1089/scd.2015.0391

Cited by 31 publications

(28 citation statements)

References 49 publications

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“…Novel data though imply also the HSC niche in driving or exacerbating aging of HSC (Li et al , 2001; Liang et al , 2005; Zhu et al , 2007). Elucidation of the mechanisms by which aging of the niche affects HSC aging will support the design of rationale therapeutic interventions to attenuate aging in hematopoiesis (Khong et al , 2015; Khatri et al , 2016). While mechanisms through which the niche regulates young HSCs have started to be elucidated (Visnjic et al , 2004; Xie et al , 2009; Méndez‐Ferrer et al , 2010; Nombela‐Arrieta et al , 2013; Bruns et al , 2014; Acar et al , 2015; Gur‐Cohen et al , 2015), data on the extent of aging of the niche and the contribution to aging of HSCs are rare.…”

Section: Introductionmentioning

confidence: 99%

Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

et al. 2017

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Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age‐related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long‐term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin‐cleaved OPN attenuates aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. Thus, our data suggest a critical role for reduced stroma‐derived OPN for HSC aging and identify thrombin‐cleaved OPN as a novel niche informed therapeutic approach for ameliorating HSC phenotypes associated with aging.

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Section: Introductionmentioning

confidence: 99%

Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

et al. 2017

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“…The engrafted stem cells always face very complicated pathological condition, such as oxidative stress, inflammation, and immune response, among which oxidative stress could play a primary role [9, 13]. A range of CNS pathologies, such as neurodegenerative diseases and neural trauma, are symbolized as oxidative stress, following the overbalanced ROS production [6, 9]. The oxidative stress consequently induces the cell damage around the lesion area, as well as the engrafted stem cell.…”

Section: Discussionmentioning

confidence: 99%

“…The pathology directs the stem cells to produce extra reactive oxygen species (ROS), which could trigger several of intracellular signalling cascades, thus leading to DNA damage and cell apoptosis and even death [9]. Therefore, study on the underlying signalling mechanism in oxidative stress could provide some evidence to rescue the engrafted stem cells from damage.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF‐κB/p65 Activation

Liu

Jiang

et al. 2016

Oxidative Medicine and Cellular Longevity

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Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2) to induce the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies.

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“…This Stem Cell Aging http://dx.doi.org/10.5772/intechopen.71764 implicates the role of ROS in perturbation of stromal cells function upon aging, which in turn affects BM's reconstitution ability in aged mice. Rejuvenation therapy using curcumin, prior to transplantation of HSCs and progenitor cells could be an efficient strategy for successful marrow reconstitution in older mice [202].…”

Section: Niche Deteriorationmentioning

confidence: 99%

Stem Cell Aging

Rožman¹,

Jazbec²,

Jež³

2018

Stem Cells in Clinical Practice and Tissue Engineering

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Stem cells persist throughout life, replacing cells lost to homeostatic turnover, injury, and disease. However, their functions decline with age, which contributes to degeneration and dysfunction. The molecular mechanisms involved in the aging of stem cells are the same as the ones involved in the aging of somatic cells, including telomere shortening, oxidative stress, epigenetic dysregulation, miRNAs changes, alterations of DNA, RNA, proteome, and various cellular organelles. Aging impacts various pathways, such as insulin/insulin-like growth factor 1 (IGF-1), mTOR, FoxO, AMP-activated protein kinase (AMPK), sirtuin, and many others, resulting in senescent stem cells that exhibit functional and numerical impairment. Stem cells have developed special mechanisms to prevent age related damage accumulation and to sustain their stemness properties, however, these mechanisms lose their effectiveness over time. The most fatal consequence of this is found in the immune system, where both innate and adaptive immunity are affected, exhibiting a plethora of defects, including increased autoimmune disease occurrence, elevated tolerance to cancer and chronic inflammatory status. Stem cell therapies call for the best quality of stem cells grafts. Stem cell products should be devoid of cells containing a senescent phenotype, thus a comprehensive knowledge of the biology behind the senescence of stem cells should be taken into account in every cell based therapy.

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Reactive Oxygen Species Limit the Ability of Bone Marrow Stromal Cells to Support Hematopoietic Reconstitution in Aging Mice

Cited by 31 publications

References 49 publications

Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF‐κB/p65 Activation

Stem Cell Aging

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