Resveratrol increases the bone marrow hematopoietic stem and progenitor cell capacity

Rimmelé, Pauline; Lofek-Czubek, Sébastien; Ghaffari, Saghi

doi:10.1002/ajh.23837

Cited by 30 publications

(21 citation statements)

References 36 publications

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“…However, the role of RES/SIRT1 on different cells remains controversial. Some studies demonstrated that RES could enhance cell survival, proliferation and multi-potent progenitor capacity, prevent senescence in cultured primary human keratinocytes, bone marrow cells and other cell types ( Ido et al, 2015 ; Rimmele et al, 2014 ). Whereas, some other evidences showed that RES could trigger cell cycle arrest, apoptosis, senescence and inhibit proliferation of cancer cells ( Jackson et al, 2016 ; Zhu et al, 2015 ) and vascular smooth muscle cells ( Guo et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs

Wang

Meng

et al. 2016

Molecules and Cells

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Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neurallineage differentiation in human umbilical cord derived MSCs (hUC-MSCs) in vitro at concentrations ranging from 0.1 to 10 μM, and whether it exerts the effects by modulating the SIRT1 signaling. Herein, we demonstrated that RES at the concentrations of 0.1, 1 and 2.5 μM could promote cell viability and proliferation, mitigate senescence and induce expression of SIRT1 and Proliferating Cell Nuclear Antigen (PCNA) while inhibit the expression of p53 and p16. However, the effects were reversed by 5 and 10 μM of RES. Furthermore, RES could promote neural differentiation in a dose-dependent manner as evidenced by morphological changes and expression of neural markers (Nestin, βⅢ-tubulin and NSE), as well as pro-neural transcription factors Neurogenin (Ngn)1, Ngn2 and Mash1. Taken together, RES exerts a dosage-dependent effect on the self-renewal and neural differentiation of hUC-MSCs via SIRT1 signaling. The current study provides a new strategy to regulate the fate of hUC-MSCs and suggests a more favorable in vitro cell culture conditions for hUCMSCs-based therapies for some intractable neurological disorders.

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Section: Introductionmentioning

confidence: 99%

Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs

Wang

Meng

et al. 2016

Molecules and Cells

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“…Other dietary compounds that have been reported to have effects on hematopoiesis include resveratrol and curcumin. Resveratrol is a naturally occurring plant-derived polyphenol and resveratrol treatment increased bone marrow HSPCs [76] as well as protected HSCs from radiation induced injury [77]. Curcumin treatment in vitro induced apoptosis in leukocytes from JAK2 V617F positive MPN patients [78].…”

Section: Dietmentioning

confidence: 99%

Impact of Host, Lifestyle and Environmental Factors in the Pathogenesis of MPN

Ramanathan

Hoover

Fleischman

2020

Cancers

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Philadelphia-negative myeloproliferative neoplasms (MPNs) occur when there is over-production of myeloid cells stemming from hematopoietic stem cells with constitutive activation of JAK/STAT signaling, with JAK2V617F being the most commonly occurring somatic driver mutation. Chronic inflammation is a hallmark feature of MPNs and it is now evident that inflammation is not only a symptom of MPN but can also provoke development and precipitate progression of disease. Herein we have considered major MPN driver mutation independent host, lifestyle, and environmental factors in the pathogenesis of MPN based upon epidemiological and experimental data. In addition to the traditional risk factors such as advanced age, there is evidence to indicate that inflammatory stimuli such as smoking can promote and drive MPN clone emergence and expansion. Diet induced inflammation could also play a role in MPN clonal expansion. Recognition of factors associated with MPN development support lifestyle modifications as an emerging therapeutic tool to restrain inflammation and diminish MPN progression.

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“…Resveratrol was shown, for example, to bind several receptors involved in hematopoiesis, including aryl hydrocarbon receptor and integrin αvβ3, both of which have been linked to HSC activity [24–26]. Furthermore, application of resveratrol via the food was able to partially restore the hematopoietic defect in vivo in a Fancd2 knockout mouse model [27], and it was shown that in vivo treatment of mice with resveratrol resulted in an increase of HSC numbers [28]. Moreover, resveratrol has been shown to inhibit cellular oxidative stress, endoplasmic reticulum stress, and lipid raft perturbation [29, 30].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Different Cytokine Conditions Reveals Resveratrol as a New Molecule for Ex Vivo Cultivation of Cord Blood-Derived Hematopoietic Stem Cells

Heinz

Ehrnström

Schambach

et al. 2015

Stem Cells Translational Medicine

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Human cord blood (CB)-derived hematopoietic stem cells (HSCs) are an interesting source for HSC transplantation. However, the number of collected CB-HSCs is often too low for one transplantation; therefore, ex vivo expansion of CB-HSCs is desirable. Current expansion protocols are based on the use of cytokine combinations, including insulin-like growth factor-binding protein 2 (IGFBP2) and angiopoietin-like proteins, or combinations with "small molecules" such as stemregenin-1. The aim of our project was to compare the potential of different CB-HSC expansion strategies side-by-side by phenotypical analysis in vitro and serial engraftment properties in NOD/SCID/IL2rg 2/2 (NSG) immunodeficient mice. We further identified resveratrol, a naturally occurring polyphenol, as a new, alternative small molecule combined with cytokines to facilitate serum-free ex vivo expansion of human CB-HSCs. The cultivation in resveratrol preserved the CB-HSC phenotype in vitro most efficiently and was ∼2 times more potent than commonly used cytokine conditions (including stem cell factor, thrombopoietin, Fms-related tyrosine kinase 3 ligand, interleukin-6) and the recently established serum-free culture, including IGFBP2 and angiopoietin-like 5. Serial transplantation studies further confirmed resveratrol to support robust multilineage engraftment in primary and secondary NSG recipients. Therefore, our work proposes resveratrol as a new small molecule for improved ex vivo culture and modification of human HSCs based on an efficient ex vivo propagation of the HSC fate. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1064-1072 SIGNIFICANCEHuman cord blood (CB)-derived hematopoietic stem cells (HSCs) are an important source for HSC transplantations but restricted in their usage because of their low numbers. In gene therapy, modifications of HSCs relies on their ex vivo modification without losing their stemness properties. Therefore, ex vivo cultivation and expansion of CB-HSCs is important for their effective application in HSC transplantation and gene therapy. Several promising protocols for serum-free cultivation of HSCs using different combinations of cytokines or so-called small molecules are described. A direct comparison was performed of three described serum-free cytokine conditions, demonstrating that the natural occurring polyphenol resveratrol is able to support ex vivo cultivation of CB-HSCs. The results show that resveratrol is an additional candidate for improving ex vivo cultures of HSCs for transplantation and gene therapeutic applications in the future.

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Resveratrol increases the bone marrow hematopoietic stem and progenitor cell capacity

Cited by 30 publications

References 36 publications

Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs

Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs

Impact of Host, Lifestyle and Environmental Factors in the Pathogenesis of MPN

Comparison of Different Cytokine Conditions Reveals Resveratrol as a New Molecule for Ex Vivo Cultivation of Cord Blood-Derived Hematopoietic Stem Cells

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