Study on the Dynamic Biological Characteristics of Sca-1<sup>+</sup>Hematopoietic Stem and Progenitor Cell Senescence

Geng, Shan; Mu, Xinyi; Chen, Xiong-Bin; Hou, Jiying; Jia, Dao‐Yong; Xu, Chunyan; Wang, Yaping

doi:10.1155/2015/954120

Cited by 6 publications

(6 citation statements)

References 14 publications

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“…Specifically, it has been reported that aberrant increases in ROS can disrupt HSC quiescence by stimulating entry into the cell cycle, which comprises the ability of the HSCs to self-renew and leads to premature exhaustion [ 34 – 36 ]. Our previous study showed that superoxide damage was accumulating in the HSCs with the natural progress of aging [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

Zhang

et al. 2017

Stem Cells International

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Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1) ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs) marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

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Section: Discussionmentioning

confidence: 99%

Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

Zhang

et al. 2017

Stem Cells International

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“…It has been observed for a long time that with advancing age, the number of HSCs decreases, which leads to deficiency in hematopoiesis and immunity in company of diseases related with aging. Our recent studies have shown that, with increasing age, the antioxidant capacity of HSCs remarkably decreases and superoxide accumulates, finally causing HSC senescence [3]. As the core component of HIM, as to whether BMMSCs can also manifest age-related senescence like HSCs can, there have been few reports concerning this.…”

Section: Introductionmentioning

confidence: 99%

Study on the Dynamic Biological Characteristics of Human Bone Marrow Mesenchymal Stem Cell Senescence

Chen

Wang

Hou

et al. 2019

Stem Cells International

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Objective. To preliminary explore the senescent dynamic changes of the bone marrow mesenchymal stem cells (BMMSCs) by human ageing and its possible mechanism. Methods. The bone marrows were harvested from healthy volunteers, and according to volunteers’ age, these were divided into group A (≤25 years), group B (26-45 years), group C (46-65 years), and group D (>65 years). Totally, the bone marrows were extracted from the posterior superior iliac spine from volunteers under aseptic conditions. Diluted with isovolumic PBS, followed by centrifugation at 1×105/cm2, cells were cultured in a 5% CO2 incubator at 37°C. After three passages, surface marker identification of hBMMSCs was tested by flow cytometry (FCM), oil red O staining was used to observe the ability of osteogenic differentiation, alkaline phosphatase (ALP) staining and the levels of osteocalcin (OST) in the supernatants were used to observe the ability of adipogenic differentiation, senescence-associated β-galactosidase (SA-β-Gal) staining was used to detect the senescent BMSCs, the ability of BMSC proliferation was detected by cell counting kit-8 (CCK-8), the distribution of the cell cycle was analyzed by flow cytometry (FCM), and malondialdehyde (MDA) content, total glutathione peroxidase, total antioxidant capacity, and total superoxide dismutase (SOD) activity was analyzed using enzymatic assay. Results. The BMSCs highly expressed CD73 and CD90, but lowly expressed CD34 and CD19/CD14. With age, osteogenic differentiation was markedly increased and audiogenic differentiation was significantly decreased. The number of SA-β-gal-positive cells was significantly increased, the proliferation ability of hBMMSCs declined, the BMSCs were held in the G1 phase, the MDA level of BMSCs was significantly increased, and total glutathione peroxidase, total antioxidant capacity, and SOD activity significantly declined. Conclusions. With age, the aging BMSCs were intensified; the mechanism may be related to oxidative damage mediated aging-related pathways.

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“…Among these 11 regulators, Cxcl12 was identified as the most dramatically increased in the GFP + cells isolated from the YS + chimeric hearts, especially after the induction of MI. Cxcl12 is of interest because it plays an important role in BM stem cell retention, mobilization, homing, and survival (Geng et al, ). Cxcl12 exerts its effects by binding the receptors Cxcr7 and Cxcr4, for which it is a unique ligand.…”

Section: Resultsmentioning

confidence: 99%

Long‐term repopulation of aged bone marrow stem cells using young Sca‐1 cells promotes aged heart rejuvenation

Dong

et al. 2019

Aging Cell

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Reduced quantity and quality of stem cells in aged individuals hinders cardiac repair and regeneration after injury. We used young bone marrow (BM) stem cell antigen 1 (Sca‐1) cells to reconstitute aged BM and rejuvenate the aged heart, and examined the underlying molecular mechanisms. BM Sca‐1+ or Sca‐1− cells from young (2–3 months) or aged (18–19 months) GFP transgenic mice were transplanted into lethally irradiated aged mice to generate 4 groups of chimeras: young Sca‐1+, young Sca‐1−, old Sca‐1+, and old Sca‐1−. Four months later, expression of rejuvenation‐related genes (Bmi1, Cbx8, PNUTS, Sirt1, Sirt2, Sirt6) and proteins (CDK2, CDK4) was increased along with telomerase activity and telomerase‐related protein (DNA‐PKcs, TRF‐2) expression, whereas expression of senescence‐related genes (p16INK4a, P19ARF, p27Kip1) and proteins (p16INK4a, p27Kip1) was decreased in Sca‐1+ chimeric hearts, especially in the young group. Host cardiac endothelial cells (GFP−CD31+) but not cardiomyocytes were the primary cell type rejuvenated by young Sca‐1+ cells as shown by improved proliferation, migration, and tubular formation abilities. C‐X‐C chemokine CXCL12 was the factor most highly expressed in homed donor BM (GFP+) cells isolated from young Sca‐1+ chimeric hearts. Protein expression of Cxcr4, phospho‐Akt, and phospho‐FoxO3a in endothelial cells derived from the aged chimeric heart was increased, especially in the young Sca‐1+ group. Reconstitution of aged BM with young Sca‐1+ cells resulted in effective homing of functional stem cells in the aged heart. These young, regenerative stem cells promoted aged heart rejuvenation through activation of the Cxcl12/Cxcr4 pathway of cardiac endothelial cells.

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Study on the Dynamic Biological Characteristics of Sca-1⁺Hematopoietic Stem and Progenitor Cell Senescence

Cited by 6 publications

References 14 publications

Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

Study on the Dynamic Biological Characteristics of Human Bone Marrow Mesenchymal Stem Cell Senescence

Long‐term repopulation of aged bone marrow stem cells using young Sca‐1 cells promotes aged heart rejuvenation

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Study on the Dynamic Biological Characteristics of Sca-1+Hematopoietic Stem and Progenitor Cell Senescence

Cited by 6 publications

References 14 publications

Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

Study on the Dynamic Biological Characteristics of Human Bone Marrow Mesenchymal Stem Cell Senescence

Long‐term repopulation of aged bone marrow stem cells using young Sca‐1 cells promotes aged heart rejuvenation

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Study on the Dynamic Biological Characteristics of Sca-1⁺Hematopoietic Stem and Progenitor Cell Senescence