Circulating platelet-progenitor cell coaggregate formation is increased in patients with acute coronary syndromes and augments recruitment of CD34+ cells in the ischaemic microcirculation

Stellos, Konstantinos; Bigalke, Boris; Pfaff, Florian; Elskamp, Alexandra; Sachsenmaier, Saskia; Zachmann, Ruben; Stamatelopoulos, Kimon; Schönberger, Tanja; Geisler, Tobias; Langer, Harald F.; Gawaz, Meinrad

doi:10.1093/eurheartj/eht131

Cited by 31 publications

(24 citation statements)

References 46 publications

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“…49 However, platelet-induced differentiation of CD34-positive progenitors into mature foam cells and endothelial cells has been described in an in vitro co-culture system, 50 which may be of particular relevance for development of atherosclerotic vascular lesions.…”

Section: Platelet/progenitor Cell Interaction and Regenerationmentioning

confidence: 99%

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Gawaz

Vogel

2013

Blood

173

129

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Besides mediating primary hemostasis and thrombosis, platelets play a critical role in tissue repair and regeneration. They regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis. Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.

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Section: Platelet/progenitor Cell Interaction and Regenerationmentioning

confidence: 99%

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Gawaz

Vogel

2013

Blood

173

129

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“…Moreover, activated platelets can also bind to injured endothelial cells. It has been reported that platelet activation starts as early as 2 mins post-reperfusion after 45 mins of ischaemia 24 , and activation and recruitment of platelets can persist for days to weeks after MI injury 9 . Our data suggest that PNV decoration resulted in a boost of CSC retention in the heart.…”

Section: Discussionmentioning

confidence: 99%

“…Various platelet surface molecules such as glycoprotein (GP)VI, GPIV, GPIb, GPIX, GPV and GPIIb/IIIa are involved in platelet recruitment 8 . It has previously been reported that platelets could form co-aggregates with circulating CD34+ progenitors in patients with acute coronary syndromes, and these co-aggregates improve prognosis by promoting peripheral recruitment of CD34+ cells in the ischaemic microcirculatory area and boosting their adhesion to the vascular lesion 9 .…”

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confidence: 97%

Targeted repair of heart injury by stem cells fused with platelet nanovesicles

et al. 2018

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Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types.

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“…It has been well established that platelets interact with and adhere to EPCs and mature endothelial cells [5,14,16,17,18,19,21,54]. Therefore, we further studied the adhesion of platelets to passage 4 OECs (which exhibited the highest anti-platelet activity in the aggregation studies) versus to CD34+ and HUVECs.…”

Section: Discussionmentioning

confidence: 99%

“…Circulating CD34+ cells contribute to cardiovascular homeostasis in a paracrine way or through differentiation into endothelial cells and smooth muscle cells in vivo [5,6,7]. These cells are increased in the peripheral blood of patients with acute myocardial infarction, and are rapidly recruited to the myocardium, mediating a protective effect of ischaemic preconditioning [5,8,9,10]. The peripheral recruitment of circulating progenitor cells is a multi-step process that includes chemoattraction, migration, adhesion, and tissue invasion [5,7].…”

Section: Introductionmentioning

confidence: 99%

Comparative Anti-Platelet Profiling Reveals a Potent Anti-Aggregatory Effect of CD34+ Progenitor Cell-Derived Late-Outgrowth Endothelial Cells in vitro

Chantzichristos

Gkrozou²,

Stellos³

et al. 2017

J Vasc Res

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Background/Aims: Platelets affect endothelial progenitor cell (EPC) functionality, inducing their differentiation into mature endothelial cells. However, it remains to be established whether EPCs can influence platelet functionality. Methods: Mononuclear proangiogenic cells (MPCs) and early outgrowth cells (EOCs) were prepared from peripheral blood mononuclear cells, whereas late-outgrowth endothelial cells (OECs) were prepared from cord blood CD34+ cells. The effect of the above cells and their supernatants on washed platelet aggregation was studied. The effect of OECs and their supernatant on the adenosine diphosphate (ADP)-induced magnitude of platelet integrin receptor α_IIbβ₃ activation and on P-selectin membrane expression was investigated. The levels of nitric oxide (NO) and prostacyclin (PGI₂) that were secreted from EOCs, OECs, and human umbilical vein endothelial cells (HUVECs) were also assessed. Results: Among all progenitors, OECs and their supernatant exhibited the most potent inhibitory activity towards platelet aggregation. Furthermore, OECs and their supernatant, but not CD34+ cells, reduced α_IIbβ₃ activation and P-selectin membrane expression. Finally, OECs secreted higher NO and PGI₂ levels than EOCs did. Conclusion: The anti-platelet effect of EPCs depends highly on the degree of their endothelial phenotype, with OECs expressing the highest potency. Therefore, the induction of OEC generation and the enhancement of their functionality in vivo could be a new approach for the treatment of patients at a high thrombotic risk.

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Circulating platelet-progenitor cell coaggregate formation is increased in patients with acute coronary syndromes and augments recruitment of CD34+ cells in the ischaemic microcirculation

Abstract: These findings imply that circulating platelet/CD34+ cell coaggregate levels are increased in ACS, especially in STEMI, which may be a novel mechanism of domiciliation of CD34+ progenitor cells to the injured microvasculature after acute myocardial infarction.

Cited by 31 publications

References 46 publications

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Targeted repair of heart injury by stem cells fused with platelet nanovesicles

Comparative Anti-Platelet Profiling Reveals a Potent Anti-Aggregatory Effect of CD34+ Progenitor Cell-Derived Late-Outgrowth Endothelial Cells in vitro

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