Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration

Shao, Hongwei; Xu, Qian; Wu, Qirui; Ma, Qi; Salgueiro, Luis; Wang, Jian’An; Eton, Darwin; Webster, Keith A.; Yu, Hong

doi:10.1111/j.1582-4934.2010.01231.x

Cited by 34 publications

(24 citation statements)

References 42 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we demonstrate that the basal Sca1 +/CXCR4 + progenitor cell levels in the bone marrow are not attenuated with age. In line with other studies [33,34], age-dependent depletion of progenitor cells is likely to be specific to a subpopulation of intermediate vascular progenitor cells (CD31 +/CD45 −) whereas the primitive progenitor subpopulations (Sca1+/c-kit+/lin−) are not affected by age. In fact, higher basal levels of bone marrow Sca1 +/CXCR4 + BMDACs were found in aged mice prior to ischemia.…”

Section: Discussionsupporting

confidence: 90%

Aging impairs ischemia-induced neovascularization by attenuating the mobilization of bone marrow-derived angiogenic cells

Lam

Lecce

Clayton

et al. 2016

IJC Metabolic & Endocrine

View full text Add to dashboard Cite

Background: Aging is associated with impaired ischemia-induced neovascularization. However, the effects of aging on bone marrow-derived angiogenic cell (BMDAC)-mediated vasculogenesis and on angiogenesis at the ischemic sites remain incompletely understood. Methods and results: Two-and 24-month old male C57Bl/6J mice were subjected to hindlimb ischemia. The levels of Sca1+/CXCR4+ BMDACs were determined post-ischemia by flow cytometry. In young mice, ischemia increased Sca1+/CXCR4+ BMDAC levels in the bone marrow and spleen at day 3 (p b 0.001) and in the circulating blood at day 7 (p b 0.01) post-ischemia. However, ischemia-induced elevation of progenitor cells was attenuated in the bone marrow, spleen and blood of old mice despite a preserved HIF-1α-mediated angiogenic response in the ischemic tissues. Irradiated young recipient mice engrafted with old bone marrow displayed reduced levels of Sca1+/CXCR4+ BMDACs in the bone marrow and circulating blood post-ischemia compared to recipients with young bone marrow. Ex vivo cultured BMDACs from old mice exhibited reduced SDF-1-stimulated migration (p b 0.01) and a decrease in JAK-2 and AKT activation. However, the intrinsic angiogenic function of BMDACs, including VEGF secretion and promotion of endothelial cell tubule formation, was preserved with aging. Furthermore, facilitated mobilization of old bone marrow-derived mononuclear cells to the ischemic hindlimb by intramuscular injection enhanced ischemia-induced neovascularization in old mice in vivo (p b 0.001). Conclusions: The age-related impairment in ischemia-induced neovascularization is largely attributable to a marked attenuation of BMDAC mobilization with a preservation of intrinsic angiogenic function with age.

show abstract

Section: Discussionsupporting

confidence: 90%

Aging impairs ischemia-induced neovascularization by attenuating the mobilization of bone marrow-derived angiogenic cells

Lam

Lecce

Clayton

et al. 2016

IJC Metabolic & Endocrine

View full text Add to dashboard Cite

show abstract

“…Similar to earlier studies (Waterstrat and Van Zant. 2009;Zediak et al 2007;Shao et al 2011), there were more myeloid lineage cells than lymphoid lineages cells in aged BM. Consequently, we sorted out B220 + , CD11b + , and Ter119 + cells which had greater differences and a higher proportion from BM A to coculture with the same bone fragments, respectively.…”

Section: Discussionmentioning

confidence: 95%

“…Min et al found that the number of common lymphoid progenitors (CLPs), pro-B cells, and pre-B cells in BM from aged mice was significantly less than that in BM from young mice (Min et al 2006). However, the number of Gr1 + /CD11b + cells in BM from aged mice is higher than that in BM from young mice (Shao et al 2011). These studies indicate that aging is associated with intrinsic HSC changes as well as changes in the microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Effect of aged bone marrow microenvironment on mesenchymal stem cell migration

Yang

Cui

et al. 2015

AGE

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are known to have many notable features, especially their multiple differentiation ability and immunoregulatory capacity. MSCs are important stem cells in the bone marrow (BM), and their characteristics are affected by the BM microenvironment. However, effects of the BM microenvironment on the properties of MSCs are not well understood. In this study, we found that BM from aged mice decreased MSC colony formation. Flow cytometry data showed that the proportion of B220 + cells in BM from aged mice was significantly lower than that in BM from young mice, while the proportion of CD11b + , CD3 + , Gr-1 + , or F4/80 + cells are on the contrary. CD11b + , B220 + , and Ter119 + cells from aged mice were not the subsets that decreased MSC colony formation. We further demonstrated that both BM from aged mice and young mice exhibited similar effects on the proliferation of murine MSC cell line C3H10T1/2. However, when cocultured with BM from aged mice, C3H10T1/2 showed slower migration ability. In addition, we found that phosphorylation of JNK (c-Jun N-terminal kinases) in C3H10T1/2 cocultured with BM from aged mice was lower than that in C3H10T1/2 cocultured with BM from young mice. Collectively, our data revealed that BM from aged mice could decrease the migration of MSCs from their niche through regulating the JNK pathway.

show abstract

“…17 During flow cytometry analysis, fluorescence of samples was monitored for a 30-second baseline, then sample aspiration was briefly paused, and 2 μl PBS, or CaCl 2 (final concentration 1mM), or CaCl 2 plus Ionomycin (final concentration 10μM) in Ca 2+ flux assay buffer were added into the samples. Ca 2+ influx was determined by measuring the change in green fluorescence intensity of the cells over time.…”

Section: Methodsmentioning

confidence: 99%

“…17 Since ApoE −/− mice spontaneously develop hypercholesterolemia and atherosclerotic lesions and have significantly shorter lifespan than wild type mice 18 , we hypothesize that atherogenic ApoE −/− mice have earlier and more severe CXCR4/SDF-1 defects than their wild type (WT) counterparts. Our rationale for the present studies is that atherosclerosis generates an aging phenotype in ApoE −/− mice and this may be associated with correspondingly reduced numbers and functions of CXCR4-positive BM progenitors.…”

Section: Introductionmentioning

confidence: 99%

Impaired CXCR4 expression and cell engraftment of bone marrow-derived cells from aged atherogenic mice

Wang

et al. 2011

Atherosclerosis

Self Cite

View full text Add to dashboard Cite

Objectives Reduced numbers and activity of circulating progenitor cells are associated with aging and have been linked with coronary artery disease. To determine the impact of aging and atherosclerotic disease on the chemotaxic activity of bone marrow derived cells (BMCs), we examined CXCR4 surface expression on BMCs from aged and atherosclerotic mice. Methods CXCR4 expression and cellular mobility were compared between BMCs of young (6-week old) ApoE null mice (ApoE−/−) and aged ApoE−/− mice that had been fed with a high-fat, high-cholesterol diet for 6-months. Results Age and atherosclerosis correlated with significantly lower surface expression of CXCR4 that was less inducible by calcium. The impaired calcium response was associated with defective calcium influx and was partially recovered by treatment with the calcium ionophore ionomycin. ApoE−/− mice fed high fat diet for 6-months had defective CXCR4 expression and SDF-1 regulation that is equivalent to that of 24-month old wild type mice. BMCs from aged, atherogenic ApoE−/− mice also displayed defective homing to SDF-1, and the animals had lower serum and bone marrow levels of SDF-1. Conclusion Evolution of atherosclerosis in ApoE−/− mice is paralleled by progressive loss of mobility of BMCs with reductions of CXCR4 expression, and reduced levels of SDF-1 in both serum and bone marrow. These changes mute the homing capability of BMCs and may contribute to the progression of atherosclerosis in this model.

show abstract

Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration

Cited by 34 publications

References 42 publications

Aging impairs ischemia-induced neovascularization by attenuating the mobilization of bone marrow-derived angiogenic cells

Aging impairs ischemia-induced neovascularization by attenuating the mobilization of bone marrow-derived angiogenic cells

Effect of aged bone marrow microenvironment on mesenchymal stem cell migration

Impaired CXCR4 expression and cell engraftment of bone marrow-derived cells from aged atherogenic mice

Contact Info

Product

Resources

About