Abstract 2: IL-10 Modulates Mobilization of Bone Marrow Endothelial Progenitor Cells and Enhances Their Survival and Angiogenic Properties in Ischemic Myocardium

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Prasanna Krishnamurthy ◽  
Melissa Thal ◽  
Suresh Verma ◽  
Eneda Hoxha ◽  
Erin Lambers ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Ischemic Myocardium ◽  
Lv Function ◽  
Dependent Manner ◽  
Myocardial Repair ◽  
Endothelial Progenitor ◽  
And Function ◽  
Deficient Mice

Endothelial progenitor cells (EPC) transplantation has been shown to enhance neovascularization and improve myocardial infarction (MI)-induced ventricular dysfunctions. However, persistent inflammation in the ischemic myocardium, adversely affect EPC survival and function, thereby compromising full benefits of EPC-mediated vascular repair. We hypothesized that modulation of IL-10 signaling in EPCs enhances their mobilization, survival and function in ischemic myocardium after MI. GFP-labeled EPC were transplanted intramyocardially after induction of MI, and the mice were treated with either saline or recombinant IL-10. EPC survival and EPC-mediated neovascularization and myocardial repair were evaluated. IL-10-treated mice showed increased number of GFP+EPCs retention that was associated with reduced EPC apoptosis in the myocardium (P<0.05). The engraftment of EPC into the vascular structures and the associated capillaries density was significantly higher in IL-10-treated mice (P<0.05). The above findings were corroborated with reduced infarct size, fibrosis and enhanced LV function (echocardiography) in IL-10+EPC group as compared to EPC+saline group. Invitro, IL-10-deficient EPCs showed higher LPS-induced apoptosis compared to WT-EPCs (P<0.05). IL-10 treatment induced VEGF expression in WT-EPCs which was abrogated by STAT3 inhibition (using curcurbitacin I). Furthermore, microRNA (miR) profile experiments identified significant increases in a number of pro-apoptotic and anti-angiogenic-related miRs in EPCs from IL-10 deficient mice. Interestingly, IL-10-deficient mice showed impaired MI-induced mobilization of bone marrow EPCs (Sca1+Flk1+ cells) into the circulation and the associated SDF-1 mRNA expression in the myocardium. Bone marrow transplantation studies involving replacement of IL-10-deficient marrow with WT marrow attenuated these effects. Invitro, LPS-induced CXCR4 expression was lower in IL-10-deficient EPCs as compared to WT-EPC. Taken together, our studies suggest that IL-10 enhances EPC mobilization, possibly in an SDF1-CXCR4 dependent manner and increased their survival and neovascularization and the associated myocardial repair, in part via activation of STAT3 signaling cascades.

Characteristics and Function of Cryopreserved Bone Marrow–Derived Endothelial Progenitor Cells

2008 ◽  
Vol 85 (4) ◽  
pp. 1361-1366 ◽  
Author(s):  
Shigetoshi Mieno ◽  
Richard T. Clements ◽  
Munir Boodhwani ◽  
Neel R. Sodha ◽  
Basel Ramlawi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor ◽  
And Function

scholarly journals Exposure to inhaled nickel nanoparticles causes a reduction in number and function of bone marrow endothelial progenitor cells

2010 ◽  
Vol 22 (sup2) ◽  
pp. 95-99 ◽  
Author(s):  
Eric N. Liberda ◽  
Azita K. Cuevas ◽  
Patricia A. Gillespie ◽  
Gabriele Grunig ◽  
Qingshan Qu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Nickel Nanoparticles ◽  
Endothelial Progenitor ◽  
And Function

Abstract 458: Critical Role of Bone Marrow Nox2-based NADPH Oxidase in Neovascularization in Response to Hindlimb Ischemia: Impact on Endothelial Progenitor Cells Function

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Norifumi Urao ◽  
Hyoe Inomata ◽  
Ha Won Kim ◽  
Ronald Mckinney ◽  
Mazooma Razvi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Nadph Oxidase ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Critical Role ◽  
Border Zone ◽  
Hindlimb Ischemia ◽  
Endothelial Progenitor ◽  
Deficient Mice

Bone marrow (BM) is the major reservoir for endothelial progenitor cells (EPCs). Postnatal neovascularization involves not only angiogenesis but also mobilization of EPCs from BM and their recruitment to the ischemic sites. We demonstrated that reactive oxygen species (ROS) derived from Nox2-based NADPH oxidase play an important role in reparative angiogenesis induced by hindlimb ischemia. However, role of Nox2-derived ROS in BM and EPC function in postnatal neovascularization is unknown. Here we show that Nox2 is the most highly expressed Nox enzymes in mouse BM cells (BMCs) and EPCs. Hindlimb ischemia of mice significantly increases Nox2 mRNA expression (2.3-fold) and ROS production (7.2-fold) in BMCs at 3 days after surgery, which is associated with an increase in number of EPC-like c-kit+Flk-1+ cells in peripheral blood (3.9-fold). Nox2-deficient mice show impairment of ischemia-induced flow recovery (68% inhibition) and significant reduction of ROS levels in BM (98% decrease) and EPC mobilization, as assessed by EPC culture assay (76% decrease) and FACS analysis of c-kit+Flk-1+ cells (33% decrease). Transplantation of wild-type (WT)-BM into Nox2-deficient mice rescues the defective neovascularization. Conversely, WT mice transplanted with Nox2-deficient BM show significant decrease of flow recovery (41% decrease) and capillary density (24% decrease) compared to WT-BM transplanted control. Intravenous infusion of WT-BM-mononuclear cells (MNCs), but not Nox2-deficient MNCs, into WT mice at 1 day after hindlimb ischemia significantly promotes neovascularization (37% increase). Infusion of fluorescent dye-labeled WT- and Nox2-deficient BMCs reveals that homing capacity of Nox2-deficient BMCs in ischemic border zone is significantly reduced (52% decrease). In vitro, VEGF-induced EPC migration (48% decrease) and BMCs invasion (68% decrease) are significantly inhibited in Nox2-deficient cells. In conclusion, Nox2-derived ROS in BM play a critical role in mobilization, homing and angiogenic capacity of EPCs, thereby promoting revascularization of ischemic tissue. Thus, NADPH oxidase in BM and EPCs is potential therapeutic targets for ischemic cardiovascular diseases.

Abstract P375: Gender-based Cardio-protective Functional Dimorphism Of Bone Marrow Endothelial Progenitor Cells And Their Exosomes: Estrogen-independent Epigenetic Mechanisms

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Charan T Gurrala ◽  
Venkata Garikipati ◽  
Zhongjian Cheng ◽  
Vandana Mallaredy ◽  
Maria Cimini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Capillary Density ◽  
Tube Formation ◽  
Ischemic Myocardium ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Endothelial Progenitor

Introduction: Estrogen or estrogen receptor-dependent mechanisms in enhancing the cardioprotective efficacy of bone marrow endothelial progenitor cells (BM-EPC) is well-established in preclinical studies. However, the efficacy of estrogen does not reflect in the data from randomized cardiovascular clinical trials, suggesting an estrogen-independent role of female BM-EPC in eliciting enhanced cardiac protection compared to males. Hypothesis: Epigenetic mechanisms may contribute to the sex-specific dimorphism of Sca-1 + /CD31 + BM-EPC in regulating cell-homing, pro-angiogenic and anti-inflammatory functions in the ischemic myocardium leading to enhanced reparative function of female progenitor cells. Methods & Results: Transplantation of GFP-BM-mononuclear cells from male and female GFP transgenic mice into the BM of lethally irradiated recipient male C57BL/6 mice resulted in the enhanced mobilization of female Sca-1 + CD31 + /GFP + BM-EPC into circulation post-MI. A higher number of female BM-EPC homed to the ischemic myocardium and significantly improved LV functions and capillary density post-MI compared to male BM-EPC. Female BM-EPC showed increased expression of bFGF, VEGFR2, SDF-1α, and IL-10 genes, thereby efficiently promoted endothelial tube formation in vitro compared to male BM-EPC. Transplantation of female BM-EPC and their exosomes into post-MI male mice improved LV cardiac function, reduced scar size, and improved capillary density compared to male BM-EPC and exosomes. Male BM-EPC showed an increased expression of G9a/Ehmt2, an H3K9me3 methyltransferase, and Dnmt3a DNA methyltransferase compared to female BM-EPC. In contrast, Kdm6b/JMJD3, H3K27me3 demethylase was highly expressed in female BM-EPC compared to males. Treatment of BM-EPC of both sexes with 17-β-estradiol did not alter the expression of Kdm6b/JMJD3. Male BM-EPC highly expressed repressive gene marks, H3K9me3, and H3K27me3 compared to females. Compared to the male, BM-EPC from female and ovariectomized (OXV) female mice showed equally high expression of angiogenic genes ANGPT-1, MDK, PLAU, Tie-2, and VEGFR2 and lower levels of inflammatory cytokines, TNFα, IFNγ, IL-1β, and CCL3. Conditioned medium from female and OVX BM-EPC equally promoted enhanced migration and tube formation of HUVEC in vitro, compared to male BM-EPC. Conclusions: An estrogen-independent epigenetic mechanism likely governs the enhanced cardiac reparative properties of female BM-EPC.

Sign in / Sign up

Export Citation Format

Share Document