Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing <scp>SDF</scp>‐1 in a rat model

Schuh, Alexander; Kroh, Andreas; Konschalla, Simone; Liehn, Elisa A.; Sobota, Radoslav M.; Biessen, Erik A.L.; Bot, Ilze; Sönmez, Tolga Taha; Schober, Andreas; Weber, Christian; Sasse, Alexander

doi:10.1111/j.1582-4934.2012.01539.x

Cited by 31 publications

(29 citation statements)

References 36 publications

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“…Since the expression of chemokines and receptors is known to be regulated by cytokines, this has been exploited to enhance the engraftment of MSCs after cell transplantation [129,130]. Priming MSCs with a cocktail of growth factors and cytokines has been found to enhance cardiac therapeutic efficacy [131].…”

Section: Preconditioning Of Stem Cells To Enhance Stem Cell Efficacymentioning

confidence: 99%

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

Shafiq

Jung

Kim³

2016

Biomaterials

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Section: Preconditioning Of Stem Cells To Enhance Stem Cell Efficacymentioning

confidence: 99%

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

Shafiq

Jung

Kim³

2016

Biomaterials

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“…For example, transplantation of endothelial progenitor cells (EPCs) was associated with increased neovascularization and improved cardiac function after MI and MI/IRI, despite variable effects on inflammation and apoptosis (Schuh et al, 2008, 2012). Overexpression of CXCL12 in transplanted EPCs further increased angiogenesis, however without significant improvement of cardiac function (Schuh et al, 2012).…”

Section: The Cxcl12/cxcr4 Axis In Cad: Identifying Potential Functionmentioning

confidence: 99%

The CXCL12/CXCR4 chemokine ligand/receptor axis in cardiovascular disease

Döring¹,

et al. 2014

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The chemokine receptor CXCR4 and its ligand CXCL12 play an important homeostatic function by mediating the homing of progenitor cells in the bone marrow and regulating their mobilization into peripheral tissues upon injury or stress. Although the CXCL12/CXCR4 interaction has long been regarded as a monogamous relation, the identification of the pro-inflammatory chemokine macrophage migration inhibitory factor (MIF) as an important second ligand for CXCR4, and of CXCR7 as an alternative receptor for CXCL12, has undermined this interpretation and has considerably complicated the understanding of CXCL12/CXCR4 signaling and associated biological functions. This review aims to provide insight into the current concept of the CXCL12/CXCR4 axis in myocardial infarction (MI) and its underlying pathologies such as atherosclerosis and injury-induced vascular restenosis. It will discuss main findings from in vitro studies, animal experiments and large-scale genome-wide association studies. The importance of the CXCL12/CXCR4 axis in progenitor cell homing and mobilization will be addressed, as will be the function of CXCR4 in different cell types involved in atherosclerosis. Finally, a potential translation of current knowledge on CXCR4 into future therapeutical application will be discussed.

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“…SDF-1α delivery to the infarct region significantly improves cardiac function after myocardial infarction. 34,35 Although these reports highlighted the importance of SDF-1α in physiological and pathophysiological reactions, most of these studies focused on the chemoattractant activity of SDF-1α and its effect on vascular function remained unclear. SDF-1α may have a crucial role in the cardiovascular disease pathology by modulating endothelial barrier integrity.…”

Section: Kobayashi Et Al Sdf-1α Enhances Endothelial Cell Barrier Intmentioning

confidence: 99%

Stromal Cell–Derived Factor-1α/C-X-C Chemokine Receptor Type 4 Axis Promotes Endothelial Cell Barrier Integrity via Phosphoinositide 3-Kinase and Rac1 Activation

Kobayashi

Sato

Kida

et al. 2014

ATVB

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Objective-Although stromal cell-derived factor (SDF)-1α is well known to modulate the mobilization of hematopoietic stem cells and endothelial progenitor cells, its effects on some pre-existing vascular functions remain unknown. We have investigated here the role of SDF-1α signaling in endothelial barrier function. Approach and Results-Treatment with SDF-1α elevated transendothelial electrical resistance and inhibited the dextran hyperpermeability elicited by thrombin in bovine aortic endothelial cells, both indicating an increase in endothelial barrier function. SDF-1α binds to 2 receptors, C-X-C chemokine receptor types 4 and 7 (CXCR4 and CXCR7). Pretreatment with a CXCR4 antagonist or CXCR4 gene depletion by small interfering RNA (siRNA) eliminated SDF-1α-induced endothelial barrier enhancement. In contrast, CXCR7 antagonist or CXCR7 gene depletion by siRNA did not influence SDF-1α-induced barrier enhancement. Pretreatment with a Gi-protein inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, or PI3K p110γ subunit gene depletion by siRNA also inhibited SDF-1α-induced barrier enhancement significantly. Western blot analysis revealed that SDF-1α phosphorylated Akt Ser473 in endothelial cells, suggesting PI3K activation. Immunostaining showed that treatment with SDF-1α formed a cortical actin rim, which was accompanied by Rac1 activation. In vivo, SDF-1α inhibited croton oil-induced vascular leakage indexed by dye extravasation, which is attenuated by a pretreatment with a CXCR4 antagonist. ). These cellular responses cause cytoskeletal rearrangement and adherens junction disassembly leading to barrier disruption. Conclusions-We9 Vascular endothelial growth factor stimulates receptor tyrosine kinase to produce NO, which disrupts cell-cell adhesion and increases barrier permeability. 10 In contrast, S1P is well known to enhance EC adhesion and barrier formation strongly via activation of its Gi protein-coupled receptor and its downstream signaling molecules, phosphoinositide 3-kinase (PI3K) and Rac1 GTPase.9,11 Because of their adhesion-promoting properties, these barrier regulatory molecules can be considered possible therapeutic targets against various types of inflammatory diseases. 8,12,13 The discovery of a novel vascular barrier modulator and the elucidation of its mechanism of action could also provide new opportunities for the treatment of inflammatory diseases.In the present study, we have attempted to elucidate whether and how SDF-1α modulates vascular endothelial permeability. We have found that the SDF-1α/CXCR4 axis promotes barrier enhancement in vascular ECs. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results SDF-1α Promotes Endothelial Barrier IntegrityAs shown in Figure 1A and 1B, SDF-1α (1-100 ng/mL) dose dependently increased transendothelial electrical resistance (TER) in bovine aortic ECs (BAECs), indicating endothelial barrier enhancement. TER reached a peak 10 minutes after SDF-1α stimulation and returned to a basal level within 75 minutes. T...

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Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF‐1 in a rat model

Cited by 31 publications

References 36 publications

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

The CXCL12/CXCR4 chemokine ligand/receptor axis in cardiovascular disease

Stromal Cell–Derived Factor-1α/C-X-C Chemokine Receptor Type 4 Axis Promotes Endothelial Cell Barrier Integrity via Phosphoinositide 3-Kinase and Rac1 Activation

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