The IGF-1 Receptor as a Therapeutic Target to Improve Endothelial Progenitor Cell Function

Fleißner, Felix; Thum, Thomas

doi:10.2119/2008-00037.fleissner

Cited by 13 publications

(9 citation statements)

References 17 publications

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“…IGF-1 is one of the most potent natural activators of the AKT signaling, a stimulator of cell growth and proliferation, and recently was recognized as an important factor to improve endothelial function of progenitor cells. 30 MSCs cultured in both VEGF and 2 kPa + VEGF conditions showed a 10-fold increase in IGF mRNA expression when compared with the PS condition (Fig. 5C).…”

Section: The Combination Of Soft Matrix and Vegf Enhances Capabilitiementioning

confidence: 93%

Synergism of Matrix Stiffness and Vascular Endothelial Growth Factor on Mesenchymal Stem Cells for Vascular Endothelial Regeneration

Wingate

Floren

Yan

et al. 2014

Tissue Engineering Part A

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Mesenchymal stem cells (MSCs) hold tremendous potential for vascular tissue regeneration. Research has demonstrated that individual factors in the cell microenvironment such as matrix elasticity and growth factors regulate MSC differentiation to vascular lineage. However, it is not well understood how matrix elasticity and growth factors combine to direct the MSC fate. This study examines the combined effects of matrix elasticity and vascular endothelial growth factor (VEGF) on both MSC differentiation into endothelial lineage and MSC paracrine signaling. MSCs were seeded in soft nanofibrous matrices with or without VEGF, and in Petri dishes with or without VEGF. Only MSCs seeded in three-dimensional soft matrices with VEGF showed significant increases in the expression of endothelial markers (vWF, eNOS, Flt-1, and Flk-1), while eliminating the expression of smooth muscle marker (SM-α-actin). MSCs cultured in VEGF alone on two-dimensional dishes showed increased expression of both early-stage endothelial and smooth muscle markers, indicating immature vascular differentiation. Furthermore, MSCs cultured in soft matrices with VEGF showed faster upregulation of endothelial markers compared with MSCs cultured in VEGF alone. Paracrine signaling studies found that endothelial cells cultured in the conditioned media from MSCs differentiated in the soft matrix and VEGF condition exhibited increased migration and formation of capillary-like structures. These results demonstrate that VEGF and soft matrix elasticity act synergistically to guide MSC differentiation into mature endothelial phenotype while enhancing paracrine signaling. Therefore, it is critical to control both mechanical and biochemical factors to safely regenerate vascular tissues with MSCs.

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Section: The Combination Of Soft Matrix and Vegf Enhances Capabilitiementioning

confidence: 93%

Synergism of Matrix Stiffness and Vascular Endothelial Growth Factor on Mesenchymal Stem Cells for Vascular Endothelial Regeneration

Wingate

Floren

Yan

et al. 2014

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…• Transduction of reprogramming factors (Oct4, Sox-2, Klf-4 and c-myc) using viral vectors • Induction of reprogramming using membrane-permeable recombinant reprogramming factors • Enhancement of reprogramming by adjustification of microenvironments using vitamin c or lower oxygen • Altering host cell machinery (e.g., disruption of p53 pathway, or altering microRNA expression) • Induction of reprogramming using small molecules (e.g., valproic acid, and 5-azacytidine) the functions of stem cells [21][22][23][24][25][26][27]. IGF sustains self-renewal and pluripotency of stem cells, promotes survival, migration and proliferation of stem cells, and reduces senescence of stem cells [28][29][30][31][32] (Fig.…”

Section: The Rationale For Employment Of Igf In Ips Cell Generationmentioning

confidence: 99%

“…The system also has powerful anti-apoptotic effects [18][19][20]. Recently, IGF and its down stream phosphoinositide 3-kinase (PI3-K) signaling pathway have been demonstrated to play a critical role in the regulation of stem cell functions, including ES, mesenchymal stem cell and progenitor cells [21][22][23][24][25][26][27]. IGF may sustain the stem cell's capacity of self-renewal and differentiation, promote their survival and migration, and prevent senescence [28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

A potential role for insulin-like growth factor signaling in induction of pluripotent stem cell formation

Li¹,

Geng²

2010

Growth Hormone & IGF Research

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“…Whether short-term treatment with IGF-I could find a role in enhancing endothelial repair following acute ischaemic insults such as myocardial infarction is not known. GH supplementation, which may have significant health benefits in elderly individuals, may provide an alternative method of increasing circulating IGF-I levels and favouring EPC-mediated vascular repair [79,148].…”

Section: Insulin Igf-i and Ghmentioning

confidence: 99%

Effects of insulin resistance on endothelial progenitor cells and vascular repair

2009

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Insulin resistance, a key feature of obesity, the metabolic syndrome and Type 2 diabetes mellitus, results in an array of metabolic and vascular phenomena which ultimately promote the development of atherosclerosis. Endothelial dysfunction is intricately related to insulin resistance through the parallel stimulatory effects of insulin on glucose disposal in metabolic tissues and NO production in the endothelium. Perturbations characteristic of insulin resistance, including dyslipidaemia, inflammation and oxidative stress, may jeopardize the structural or functional integrity of the endothelium. Recent evidence suggests that endothelial damage is mitigated by endogenous reparative processes which mediate endothelial regeneration. EPCs (endothelial progenitor cells) are circulating cells which have been identified as mediators of endothelial repair. Several of the abnormalities associated with insulin resistance, including reduced NO bioavailability, increased production of ROS (reactive oxygen species) and down-regulation of intracellular signalling pathways, have the potential to disrupt EPC function. Improvement in the number and function of EPCs may contribute to the protective actions of evidence-based therapies to reduce cardiometabolic risk. In the present article, we review the putative effects of insulin resistance on EPCs, discuss the underlying mechanisms and highlight potential therapeutic manoeuvres which could improve vascular repair in individuals with insulin resistance.

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The IGF-1 Receptor as a Therapeutic Target to Improve Endothelial Progenitor Cell Function

Cited by 13 publications

References 17 publications

Synergism of Matrix Stiffness and Vascular Endothelial Growth Factor on Mesenchymal Stem Cells for Vascular Endothelial Regeneration

Synergism of Matrix Stiffness and Vascular Endothelial Growth Factor on Mesenchymal Stem Cells for Vascular Endothelial Regeneration

A potential role for insulin-like growth factor signaling in induction of pluripotent stem cell formation

Effects of insulin resistance on endothelial progenitor cells and vascular repair

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