High-resolution mass spectrometric analysis of the secretome from mouse lung endothelial progenitor cells

Hemmen, Katherina; Reinl, Tobias; Buttler, Kerstin; Behler, Friederike; Dieken, Hauke; Jänsch, Lothar; Wilting, Jörg; Weich, Herbert A.

doi:10.1007/s10456-011-9200-x

Cited by 20 publications

(15 citation statements)

References 27 publications

(28 reference statements)

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“…The identification of the array of factors secreted by EPC is still object of intense investigation [12], [15], [31]. We and others have previously documented the presence of several growth factors and cytokines in EPC-CM [7], [11] and in the present work we consistently report the increased level of angiogenic factors in EPC-CM as result of hypoxic conditioning.…”

Section: Discussionsupporting

confidence: 82%

The Secretome of Endothelial Progenitor Cells Promotes Brain Endothelial Cell Activity through PI3-Kinase and MAP-Kinase

et al. 2014

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BackgroundAngiogenesis and vascular remodelling are crucial events in tissue repair mechanisms promoted by cell transplantation. Current evidence underscores the importance of the soluble factors secreted by stem cells in tissue regeneration. In the present study we investigated the effects of paracrine factors derived from cultured endothelial progenitor cells (EPC) on rat brain endothelial cell properties and addressed the signaling pathways involved.MethodsEndothelial cells derived from rat brain (rBCEC4) were incubated with EPC-derived conditioned medium (EPC-CM). The angiogenic response of rBCEC4 to EPC-CM was assessed as effect on cell number, migration and tubular network formation. In addition, we have compared the outcome of the in vitro experiments with the effects on capillary sprouting from rat aortic rings. The specific PI3K/AKT inhibitor LY294002 and the MEK/ERK inhibitor PD98059 were used to study the involvement of these two signaling pathways in the transduction of the angiogenic effects of EPC-CM.ResultsViable cell number, migration and tubule network formation were significantly augmented upon incubation with EPC-CM. Similar findings were observed for aortic ring outgrowth with significantly longer sprouts. The EPC-CM-induced activities were significantly reduced by the blockage of the PI3K/AKT and MEK/ERK signaling pathways. Similarly to the outcome of the rBCEC4 experiments, inhibition of the PI3K/AKT and MEK/ERK pathways significantly interfered with capillary sprouting induced by EPC-CM.ConclusionThe present study demonstrates that EPC-derived paracrine factors substantially promote the angiogenic response of brain microvascular endothelial cells. In addition, our findings identified the PI3K/AKT and MEK/ERK pathways to play a central role in mediating these effects.

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Section: Discussionsupporting

confidence: 82%

The Secretome of Endothelial Progenitor Cells Promotes Brain Endothelial Cell Activity through PI3-Kinase and MAP-Kinase

et al. 2014

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“…The EPC secretome has recently been analyzed and found to contain at least 35 proteins known to relate to endothelial cell biology and angiogenesis [81]. As discussed above, EPCs also appear to exert immunomodulatory effects.…”

Section: Therapeutic Potential Of Stem Cells For Ali/ardsmentioning

confidence: 99%

Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?

et al. 2012

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A growing understanding of the complexity of the pathophysiology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), coupled with advances in stem cell biology, has led to a renewed interest in the therapeutic potential of stem cells for this devastating disease. Mesenchymal stem cells appear closest to clinical translation, given the evidence that they may favourably modulate the immune response to reduce lung injury, while maintaining host immune-competence and also facilitating lung regeneration and repair. The demonstration that human mesenchymal stem cells exert benefit in the endotoxin-injured human lung is particularly persuasive. Endothelial progenitor cells also demonstrate promise in reducing endothelial damage, which is a key pathophysiological feature of ALI. Embryonic and induced pluripotent stem cells are at an earlier stage in the translational process, but offer the hope of directly replacing injured lung tissue. The lung itself also contains endogenous stem cells, which may ultimately offer the greatest hope for lung diseases, given their physiologic role in replacing and regenerating native lung tissues. However, significant deficits remain in our knowledge regarding the mechanisms of action of stem cells, their efficacy in relevant pre-clinical models, and their safety, particularly in critically ill patients. These gaps need to be addressed before the enormous therapeutic potential of stem cells for ALI/ARDS can be realised.

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“…53 Conditioned medium (CM) from EPC cultures was analyzed using enzyme-linked immunosorbent assay, 11,54 cytokine antibody array, 50,55 and nanoflow liquid chromatographic mass spectrometry. 53,56 Paracrine Factors of E-EPCs E-EPCs derive from a myeloid lineage and appear as end cells for their little proliferative capacity. It might be of great value to reveal the paracrine effect of E-EPCs, and results from recent studies are convincing.…”

Section: Factors Secreted By Epcs and Detection Methodsmentioning

confidence: 99%

Endothelial Progenitor Cells

Zhu²,

Lu³

et al. 2012

Journal of Cardiovascular Pharmacology

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Endothelial progenitor cells were initially considered to radically alter the concepts of adult tissue angiogenesis for their contribution of incorporation into new blood vessels. Nevertheless, controversy arises over their mechanism of action due to rare cell population and decreased number and impaired activity under pathological changes. Recent studies show that endothelial progenitor cells also function in a paracrine manner by secreting multiple cytokines and growth factors, but the beneficial paracrine signals remain partially unidentified. In this review, we provide an overview of varieties and signal pathways of factors secreted by endothelial progenitor cells and further present the prospect of new ways to encourage cardiovascular protection such as neovascularization, reendothelialization of larger vessels, and myocardial remodeling based on the paracrine factors.

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High-resolution mass spectrometric analysis of the secretome from mouse lung endothelial progenitor cells

Cited by 20 publications

References 27 publications

The Secretome of Endothelial Progenitor Cells Promotes Brain Endothelial Cell Activity through PI3-Kinase and MAP-Kinase

The Secretome of Endothelial Progenitor Cells Promotes Brain Endothelial Cell Activity through PI3-Kinase and MAP-Kinase

Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?

Endothelial Progenitor Cells

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