Evaluation of Tissue Factor Bearing Microparticles as Biomarkers in Allogeneic Stem-Cell Transplantation

Rop, Christiane De; Stadler, Michael; Buchholz, Stefanie; Eisert, R.; Ganser, Arnold; Trummer, Arne

doi:10.1097/tp.0b013e318223307f

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…As reported in other transplantations (26,27,38), baseline post-transplantation endothelial CD105 + -MVs were reduced in all subsets (p<0.05). In PS patients a 2-fold elevation occurred 78 days before the β-score drop (0.56±0.08 vs. baseline: 0.23±0.04nM, p<0.01) and 79.8 days before in F (0.54±0.05 vs. baseline: 0.17±0.05nM, p<0.01) (Figure 3B, Table2, SuppTable7).…”

Section: Cd105-bearing Endothelial MV Plasma Concentrationssupporting

confidence: 84%

“…Circulating MVs of endothelial origin or bearing TF are promising tools to monitor the immunosuppressiondriven endothelial damage and graft dysfunction after renal transplantation (24,25), and identify a worsening cardiovascular outcome (26). In recipients of stem cells, circulating TF + -MVs are predictive of worsening outcome (27).…”

Section: Accepted Article Accepted Articlementioning

confidence: 99%

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Assessment of plasma microvesicles to monitor pancreatic islet graft dysfunction: Beta cell- and leukocyte-derived microvesicles as specific features in a pilot longitudinal study

Amoura

El-Ghazouani

Kassem

et al. 2020

American Journal of Transplantation

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Markers of early pancreatic islet graft dysfunction and its causes are lacking. We monitored 19 T1D islet-transplanted patients for up to 36 months following last islet injection. Patients were categorized as Partial (PS) or complete (S) Success, or Graft Failure (F), using the βscore as an indicator of graft function. F was the subset reference of maximum worsened graft outcome. To identify the immune, pancreatic, and liver contribution to the graft dysfunction, the cell origin and concentration of circulating micro vesicles (MVs) were assessed, including MVs from insulin-secreting ß-cells typified by PSA-NCAM, and data were compared with values of the β-score. Similar ranges of PSA-NCAM + -MVs were found in healthy volunteers and S patients, indicating minimal cell damage. In PS, a 2-fold elevation in PSA-NCAM + -MVs preceded each β-score drop along with a concomitant rise in insulin needs, suggesting ß-cell damage or altered function. Significant elevation of liver ASGPR + -MVs, endothelial CD105 + -MVs, neutrophil CD66b + -MVs, monocyte CD 14 + -MVs, Accepted Article Accepted Article This article is protected by copyright. All rights reserved. and T4 lymphocyte CD4 + -MVs occurred before each -score drop, CD8 + -MVs increased only in F, B lymphocyte CD19 + -MVs remained undetectable. In conclusion, PSA-NCAM + -MVs are non-invasive early markers of transplant dysfunction, while ASGPR + -MVs signal host tissue remodeling. Leukocyte MVs could identify the cause of graft dysfunction.

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Section: Cd105-bearing Endothelial MV Plasma Concentrationssupporting

confidence: 84%

Section: Accepted Article Accepted Articlementioning

confidence: 99%

Assessment of plasma microvesicles to monitor pancreatic islet graft dysfunction: Beta cell- and leukocyte-derived microvesicles as specific features in a pilot longitudinal study

Amoura

El-Ghazouani

Kassem

et al. 2020

American Journal of Transplantation

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“…Procoagulant MPs were identified in the plasma of patients with islet graft rejection, possibly in association with IR, 14,15 while elevated TF + -MPs characterized myocardial rejection 16 and worsened outcome in stem cell transplantation. 17 Pro-inflammatory MPs from platelets, lymphocytes and monocytes would favour leucocyte recruitment at the inflamed endothelium surface known to expose adhesion molecules, like ICAM-1, VCAM-1 and E-selectin, thereby accelerating IRI. [18][19][20] Interestingly, a recent report describes a cardio-splenic axis that augments infarct size during post-ischaemic reperfusion via leucocyte activation and the recruitment of spleen neutrophils at site of the ischaemic heart, 21 eventually favouring local endothelial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Significance of neutrophil microparticles in ischaemia‐reperfusion: Pro‐inflammatory effectors of endothelial senescence and vascular dysfunction

Habhab

Altamimy

Abbas

et al. 2020

J Cellular Molecular Medi

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Endothelial senescence is an emerging cause of vascular dysfunction. Because microparticles are effectors of endothelial inflammation and vascular injury after ischaemia‐reperfusion, we examined leucocyte‐derived microparticles of spleen origin as possible contributors. Microparticles were generated from primary rat splenocytes by either lipopolysaccharide or phorbol‐myristate‐acetate/calcium ionophore, under conditions mimicking innate and adaptive immune responses. Incubation of primary porcine coronary endothelial cells with either type of microparticles, but not with those from unstimulated splenocytes, leads to a similar threefold raise in senescence‐associated β‐galactosidase activity within 48 hours, indicating accelerated senescence, to endothelial oxidative stress, and a fivefold and threefold increase in p21 and p16 senescence markers after 24 hours. After 12‐hour incubation, the endothelial‐dependent relaxation of coronary artery rings was reduced by 50%, at distinct optimal microparticle concentration. In vitro, microparticles were pro‐thrombotic by up‐regulating the local angiotensin system, by prompting tissue factor activity and a secondary generation of pro‐coagulant endothelial microparticles. They initiated an early pro‐inflammatory response by inducing phosphorylation of NF‐κB, MAP kinases and Akt after 1 hour, and up‐regulated VCAM‐1 and ICAM‐1 at 24 hours. Accordingly, VCAM‐1 and COX‐2 were also up‐regulated in the coronary artery endothelium and eNOS down‐regulated. Lipopolysaccharide specifically favoured the shedding of neutrophil‐ and monocyte‐derived microparticles. A 80% immuno‐depletion of neutrophil microparticles reduced endothelial senescence by 55%, indicating a key role. Altogether, data suggest that microparticles from activated splenocytes prompt early pro‐inflammatory, pro‐coagulant and pro‐senescent responses in endothelial cells through redox‐sensitive pathways. The control of neutrophil shedding could preserve the endothelium at site of ischaemia‐reperfusion–driven inflammation and delay its dysfunction.

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“…The ambition for future is to prove whether measuring MP levels can really help to improve patient's treatment or even survival. In their article (6), the investigators present the feasibility to use MP analyzing in this way.…”

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confidence: 98%

Relevance of Measuring Circulating Microparticles During Organ and Stem-Cell Transplantation

Rank¹

2011

Transplantation

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M icroparticles (MP) were first described by Wolf (1) as "cell dust in human plasma" in 1967. This "dust" is derived from circulating cells and endothelial cells after cell activation or apoptosis and contains vesicles with a diameter between 0.1 and 1.0 m. During MP formation, the asymmetric order of cell membrane collapses, and negative phospholipids such as phosphatidylserine reach the MP surface were they can usually be detected by annexin V. Mechanism of MP release is shown in Figure 1. Furthermore, MP are composed of lipids and proteins transferred from their "parent cells." This helps to determine the origin of MP: endothelial-derived MP for example carry tissue factor on their surface and are positive for CD31 and CD144. In healthy humans, most MP in plasma are CD61 positive and were believed to be platelet derived; but in recent years, there is more and more evidence that they are mainly released from megakaryocytes directly into circulation together with platelets. These MP are important initiators for plasmatic coagulation by presenting a negatively charged phospholipid surface with binding sites for several different coagulation factors (2). In patients suffering from Scott's syndrome, there is an impairment of MP formation resulting in a bleeding disorder with hematoma and bleeding complications. On the other side, increased numbers of MP derived from platelets and megakaryocytes are associated with a hypercoagulant status like in patients with venous thrombosis (3). In addition to their rule in hemostasis, MP are involved in intercellular transport and transfer of bioactive molecules, cell activation, and inflammation: endothelial cell-derived MP activate granulocytes, induce expression of tissue factor in monocytes, and influence angiogenesis through metalloproteinase. In turn, MP from leukocytes stimulate the endothelium. So it is not surprising that in various disorders such as diabetes, hypertension, or malignancies, enhanced plasma levels of different MP can be found reflecting the apoptotic and activation status of the parent's cell population.From a clinical point of view, the question is how can we use the information given from individual MP pattern can be used for patient's diagnosis or prognosis? Especially for organ and hematopoetic stem-cell transplantation measuring MP in plasma provides the opportunity to get information about activation status of different cell types. In this context, it seems helpful to determine MP levels at different points of time during transplantation period to be able to interpret increased or decreased values at certain points of time. MP levels in patients before transplantation regularly differ from healthy humans as these patients mostly suffer from severe disorders. For example, patients with end-stage renal failure show increased MP levels during the time of hemodialysis normalized MP levels after uncomplicated renal transplantation (4). Similar developments were found in patients with hepatitis C undergoing liver transplantation. MP levels usually norma...

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Evaluation of Tissue Factor Bearing Microparticles as Biomarkers in Allogeneic Stem-Cell Transplantation

Abstract: Tissue factor bearing MPs might be useful biomarkers for risk stratification in allo-SCT patients and further studies should investigate their origin, functional properties, and optimal cut-off values.

Cited by 8 publications

References 35 publications

Assessment of plasma microvesicles to monitor pancreatic islet graft dysfunction: Beta cell- and leukocyte-derived microvesicles as specific features in a pilot longitudinal study

Assessment of plasma microvesicles to monitor pancreatic islet graft dysfunction: Beta cell- and leukocyte-derived microvesicles as specific features in a pilot longitudinal study

Significance of neutrophil microparticles in ischaemia‐reperfusion: Pro‐inflammatory effectors of endothelial senescence and vascular dysfunction

Relevance of Measuring Circulating Microparticles During Organ and Stem-Cell Transplantation

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