LIF maintains progenitor phenotype of endothelial progenitor cells via Krüppel-like factor 4

Li, Xiaoxia; Song, Yimeng; Wang, Dawei; Fu, Cheng; Zhu, Zhenjiu; Han, Yingying; Li, Chenghong; Wang, Nanping; Zhu, Yi

doi:10.1016/j.mvr.2012.07.005

Cited by 7 publications

(9 citation statements)

References 46 publications

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“…This was in line with previous findings showing that Klf4 is upregulated by shear stress [18], a typical EC differentiation stimulus, and that Klf4 regulates eNOS [10,14,31,37] and VE-cadherin expression [16] and inhibits SMC maturation [38]. Furthermore, a recent publication showed that Klf4 played a fundamental role in the maintenance of the vascular phenotype of endothelial progenitor cells [39]. Interestingly, the Klf4-induced canonical Wnt pathway activation and effect on differentiation was mimicked by LiCl, a Wnt activator.…”

Section: Discussionsupporting

confidence: 91%

c-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway

et al. 2015

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The development of decellularised scaffolds for small diameter vascular grafts is hampered by their limited patency, due to the lack of luminal cell coverage by endothelial cells (EC) and to the low tone of the vessel due to absence of a contractile smooth muscle cells (SMC). In this study, we identify a population of vascular progenitor c-Kit+/Sca-1- cells available in large numbers and derived from immuno-privileged embryonic stem cells (ESCs). We also define an efficient and controlled differentiation protocol yielding fully to differentiated ECs and SMCs in sufficient numbers to allow the repopulation of a tissue engineered vascular graft. When seeded ex vivo on a decellularised vessel, c-Kit+/Sca-1-derived cells recapitulated the native vessel structure and upon in vivo implantation in the mouse, markedly reduced neointima formation and mortality, restoring functional vascularisation. We showed that Krüppel-like transcription factor 4 (Klf4) regulates the choice of differentiation pathway of these cells through β-catenin activation and was itself regulated by the canonical Wnt pathway activator lithium chloride. Our data show that ESC-derived c-Kit+/Sca-1-cells can be differentiated through a Klf4/β-catenin dependent pathway and are a suitable source of vascular progenitors for the creation of superior tissue-engineered vessels from decellularised scaffolds.

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Section: Discussionsupporting

confidence: 91%

c-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway

et al. 2015

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“…Fibrin is a known inducer of Nanog expression leading to increased early EPC cell viability and a reduction in mature endothelial markers of CD144, CD31, and vWF (Table 1) [134]. Furthermore, ECFCs isolated from PB were analysed for the expression of self-renewal genes; Nanog was not detected which is not unexpected as these cells are largely indistinguishable from mature ECs further pointing to a role of Nanog in maintaining the primitive status of EPCs, similar to the roles of Klf4 and Id1 [76,96,135]. Notably, there is increasing evidence to support agonistinduced enhanced Nanog expression in mature ECs.…”

Section: 7mentioning

confidence: 88%

“…Interestingly, Klf4 appears to have an opposing but complementary role to Klf2 in the regulation of EPC differentiation. Reduced differentiation potential of ECFCs was evident following costimulation with VEGF and leukemia inhibitory factor (LIF), a member of the IL-6 family, due to Akt activation and a subsequent increase in Klf4 expression (Figure 4) [76].…”

Section: Kruppel-like Factorsmentioning

confidence: 99%

Regulation of EPCs: The Gateway to Blood Vessel Formation

Parham

Pitson

Bonder

2014

New Journal of Science

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Endothelial progenitor cells (EPCs) are primitive endothelial precursors which are known to functionally contribute to the pathogenesis of disease. To date a number of distinct subtypes of these cells have been described, with differing maturation status, cellular phenotype, and function. Although there is much debate on which subtype constitutes the true EPC population, all subtypes have endothelial characteristics and contribute to neovascularisation. Vasculogenesis, the process by which EPCs contribute to blood vessel formation, can be dysregulated in disease with overabundant vasculogenesis in the context of solid tumours, leading to tumour growth and metastasis, and conversely insufficient vasculogenesis can be present in an ischemic environment. Importantly, it is widely known that transcription factors tightly regulate cellular phenotype and function by controlling the expression of particular target genes and in turn regulating specific signalling pathways. This suggests that transcriptional regulators may be potential therapeutic targets to control EPC function. Herein, we discuss the observed EPC subtypes described in the literature and review recent studies describing the role of a number of transcriptional families in the regulation of EPC phenotype and function in normal and pathological conditions.

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“…100 Yamaguchi et al (2003) Early EPC SDF-1 decreased apoptosis caused by serum starvation. VEGF 100 Li et al (2012) Late EPC VEGF 100 ng/ml had no significant effect on apoptosis. 10-100 D'Atri et al 2011 CD34 + VEGF 10-100 ng/ml did not reduce apoptosis occurring in acidic medium pH 6.5.…”

Section: Capillary-tube Like Formationmentioning

confidence: 93%

“…There was no migration into the right chamber or change in cell morphology for the control group. Li et al (2012) Human cord blood from umbilical cords of newborns was collected with the use of heparin (20 U/ml) from donors. MNCs were isolated by density gradient centrifugation with Ficoll (1.077 g/ml) and plated on plates coated with fibronectin (50 mg/ml).…”

Section: Types Of Cells Usedmentioning

confidence: 99%

Influence of growth factors and cytokines on angiogenic function of endothelial progenitor cells: a review ofin vitrohuman studies

Peplow

2014

Growth Factors

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Growth factors and cytokines released at sites of injury and inflammation play an important role in stimulating endothelial progenitor cell (EPC) migration to these sites. A comparative analysis of the literature shows under neutral in vitro conditions (pH 7.4), several growth factors and cytokines influenced favorably indices of EPC angiogenic function. They included SDF-1, VEGF, PlGF, FGF-2, NGF and IL-1β. Others, e.g. TNF-α, have an unfavorable influence. SDF-1 and VEGF in combination increased chemotactic cell migration and reduced apoptosis caused by serum starvation. Under acidic conditions (pH 6.5), the biological activity of certain growth factors may be impaired, although TPO, SCF and IL-3 were each able to rescue EPCs from acidic exposure apoptosis, a combination of these three factors stimulated cell proliferation and prevented apoptosis. Possible combinations of growth factors and cytokines together with EPC transplantation may provide for a greater extent of vessel repair and new vessel formation.

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LIF maintains progenitor phenotype of endothelial progenitor cells via Krüppel-like factor 4

Cited by 7 publications

References 46 publications

c-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway

c-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway

Regulation of EPCs: The Gateway to Blood Vessel Formation

Influence of growth factors and cytokines on angiogenic function of endothelial progenitor cells: a review ofin vitrohuman studies

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