Mehran Ghasemzadeh

Iranian Blood Transfusion Organization · High Institute for Research and Education in Transfusion Medicine,

X-irradiation of blood products is an alternative for gamma-ray to prevent post-transfusion GvHD. However, commercial X-irradiators are not widely available while little is known about their safety and efficacy for platelet products. This study introduces an efficient, accessible and cost-effective “X irradiation system” for platelet concentrates (...

During coronary artery bypass grafting (CABG), the surgical procedure, particularly the manipulation of the major arteries of the heart, induces a significant inflammatory state that may compromise platelet function to the extent that platelet transfusion is required. Given stored platelets as a major source of biological mediators, this study inve...

Background: Platelet storage is generally complicated by deleterious changes, among which reduction of ristocetin-induced platelet aggregation (RIPA) has a poorly understood mechanism. This study aimed to elucidate the mechanistic roles of all the possible players in this process including the status of GPIbα (its platelet expression/total content...

Background: Although gamma-irradiation to platelet products is a standard method to prevent the risk of TA-GVHD in vulnerable recipients, it induces some proteomic and redox changes, of which irradiation-induced ROS increments may potentiate platelet mitochondrial dysfunction. However, whether these changes cause platelet apoptosis, or affect thei...

Background: HLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex w...

Activated platelets are involved in the atherogenic stage of atherosclerosis, while they can also progress it to atherothrombosis which may cause an ischemic state and organ failure. In general, coronary artery disease (CAD) is considered as common and severe clinical consequence of atherosclerosis, manifesting as a chronic inflammatory condition w...

Background HLA-E binding to NKG2A/CD94 induces inhibitory signals that modulate NK cells cytotoxicity against infected targets. HCV-derived peptides stabilize HLA-E molecule that favours its higher expression. However, HLA-E stability and expression vary in different genotypes where the presence of HLA-E*01:03 allele is associated with higher HLA-E...

Platelet-leukocyte crosstalk is commonly manifested by reciprocal links between thrombosis and inflammation. Platelet thrombus acts as a reactive matrix that recruits leukocytes to the injury site where their massive accumulation, activation and migration promote thrombotic events while triggering inflammatory responses. As a life-threatening condi...

Background Continuous agitation during storage slows down the platelet storage lesions. However, in special circumstances, manual-mixing can be alternatively used to store products for short time periods without compromising platelet quality. Based on this finding, and given the role of shear stress in modulating receptor expression, we were intere...

Irradiation of platelet products is generally used to prevent transfusion-associated graft-versus-host disease (TA-GvHD) as well as transfusion-transmitted infections. As an essential prerequisite, gamma-irradiation of blood products prior to transfusion is required in patients who may develop TA-GVHD. Most studies suggest that gamma irradiation ha...

The global outbreak of coronavirus-2019 (COVID-19) still claims more lives daily around the world due to the lack of a definitive treatment and the rapid tendency of virus to mutate, which even jeopardizes vaccination efficacy. At the forefront battle against SARS-CoV-2, an effective innate response to the infection has a pivotal role in the initia...

Background As a method with insignificant adverse effects on in vitro quality of platelet concentrates (PCs), gamma irradiation is applied to abrogate the risk of transfusion‐associated graft‐vs‐host disease in vulnerable recipients. However, there is some evidence of lower posttransfusion responses and proteomic alterations in gamma‐irradiated pla...

Background Upon vascular damage, the exposed subendothelial matrix recruits circulating platelets to site of injury while inducing their firm adhesion mainly via GPVI-collagen interaction. GPVI also supports aggregatory and pro-coagulant functions in arterial shear rate even on the matrix other than collagen. Reactive oxygen species (ROS) modulate...

Thrombosis involves different stages including platelet adhesion to the site of injury, aggregatory events governed by integrin activation, pro-inflammatory responses recruiting leukocytes and finally, pro-coagulant activity which results in fibrin generation and clot formation. As important signaling agents, reactive oxygen species (ROS) reduce th...

Upon vascular damage, the exposure of sub-endothelial matrix to circulating platelets causes their firm adhesion and spreading on the site of injury mainly via GPVI-collagen interaction. Whilst reactive oxygen species (ROS) modulate this stage of thrombosis, augmented oxidant stress also disturbs platelet functions. Stored-dependent platelet lesion...

Background: Upon vascular damage, the exposed subendothelial matrix recruits circulating platelets to site of injury while inducing their firm adhesion mainly via GPVI-collagen interaction. GPVI also supports aggregatory and pro-coagulant functions in arterial shear rate even on the matrix other than collagen. Reactive oxygen species (ROS) modulate...

Physiologically, upon platelet activation, uncontrolled propagation of thrombosis is prevented by regulating mechanisms which affect the expression and function of either platelet adhesion receptors or integrins. Receptor ectodomain shedding is an elective mechanism which is mainly involved in down-regulation of adhesion receptors GPIbα and GPVI. P...

Upon platelet activation, inside-out signals synergistically induced by a variety of agonists and adhesion molecules can enhance the affinity of platelet main integrin, αIIbβ3 to its ligands. Integrin ligation with fibrinogen induces potent signals which develop platelet function including aggregation, release and spreading of which platelet spread...

Ehteramolsadat Hosseini, Mehran Ghasemzadeh Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine Tehran, Iran Introduction: So far, several lines of evidence showed the importance of intra-platelet ROS generation in the modulation of platelet activation and thrombus formation. This study aimed to eva...

Mehran Ghasemzadeh, Ehteramolsadat Hosseini ;Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine Tehran, Iran Introduction: Platelet activation was shown to be associated with microparticle release. However, during platelet storage, microvesiculation may also occur by the ignition of the apoptotic...

BACKGROUND Platelet storage is often complicated by deleterious changes that are started by reversible activation of the cells and can lead to procoagulant function and apoptosis during longer periods of storage. Given that increasing levels of reactive oxygen species (ROS) generation are associated with platelet activation and apoptosis, our study...

Platelet receptor GPVI plays an important role in platelet firm adhesion to site of vascular injury. Receptor ligation with collagen, in company with other agonist/receptor interactions, augments inside out signaling pathways leading to platelet aggregation and thrombus formation. As GPVI expression is significantly modulated by ectodomain shedding...

Introduction: Adhesion to different matrixes is commonly used to evaluate platelet functional capacity. Platelet adhesion is initially modulated by platelet adhesive receptors including GPIbα and GPVI, while induced inside-out signals downstream of these receptors also activate integrin αIIbβ3 which mainly augment platelet activation, aggregation a...

So far, substantial attentions have been attracted to the application of mesenchymal stem or stromal cells (MSCs) in different therapeutic approaches. Although human bone marrow is commonly considered as a major source for MSCs, having an invasive collection method, ethical consideration and donor availability create a challenge for scientists, lea...

Objectives: The in vitro treatment of tumor cells with platelet (Plt) causes inhibition of tumor cell growth, although mechanism of this effect is not clear yet. Induction of apoptosis has been proposed as a mechanism of Plt effects on tumor cells. The purpose of this study was to clarify the role of Plts and Plt-derived components in the inductio...

Platelets storage lesion is mainly orchestrated by platelet activating signals during storage. Reactive oxygen species (ROS) are being considered as important signaling molecules modulating platelet function while their production has also been shown to be augmented by platelet activation. This study investigated to what extent endogenous ROS gener...

Background: Platelet stimulation with agonists is accompanied by the generation of reactive oxygen species (ROS) which promotes further platelet activation and aggregation. Considering different cell populations in platelet concentrates (PCs), this study investigates the correlation of ROS generation with the expression and release of platelet act...

Background: Regardless of different sources, methods or devices which are applied for preparation of therapeutic platelets, these products are generally isolated from whole blood by the sedimentation techniques which are based on PRP or buffy coat (BC) separation. As a general fact, platelet preparation and storage are also associated with some de...

Introduction: It has been reported that platelets can eradicate tumor cells in vitro, although the mechanism of this effect has not been determined. The effect of platelets on the induction of apoptosis in tumor cells is largely unknown. Materials and methods: To investigate this effect, two human hematologic cell lines, K562 and Daudi, were indepe...

Abstract Background Upon platelet stimulation with agonists, reactive oxygen species (ROS) generation enhances platelet activation and granule release. Whether ROS generation during platelet storage could be directly correlated with the expression of proinflammatory molecules and granule release has been investigated in this study. Material and me...

Considering umbilical cord blood (UCB) as a rich source of hematopoietic stem cells, we introduced a cost-effective approach to expand CD3depleted UCB-MNCs into functional NK cells. CD3depleted UCB-MNCs were expanded in the presence or absence of a feeder [bone marrow stem cells (BMSCs) or osteoblasts], with or without cytokines and their different...

Blood transfusion is commonly implemented to manage life and health-threatening conditions on a rapid and short-term basis. Over the years, ongoing technical advances have dramatically improved transfusion medicine to provide more safety and effectiveness. However, transfusion is still complicated with different adverse events that mainly induced b...

Background: Platelet storage is complicated by deleterious changes that cause progressive structural and functional damages, so-called platelet storage lesion (PSL). PSL is commonly manifested by augmented platelet activation which is also associated with the increased levels of reactive oxygen species (ROS). Whether ROS generation increases during...

Context: The major motivation for the preparation of the plasma derived biological medicine was the treatment of casualties from the Second World War. Due to the high expenses for preparation of plasma derived products, achievement of self-sufficiency in human plasma biotechnological industry is an important goal for developing countries. Evidence...

Platelet storage is associated with deleterious changes leading to the loss of platelet reactivity and response. During storage, platelets experience increased expression and shedding of P-selectin and CD40L as specific markers of platelet activation, whereas GPIbα decreases due to ectodomain shedding. As an important adhesive receptor, GPVI contri...

Background: Human leukocyte antigen E is a member of non-classical HLA class I. Interaction between HLA-E molecule on the target cells and inhibitory CD94/NKG2A receptor on the cell surface of natural killer (NK) cells has an important role in the regulation of immune system against pathogens; therefore different cell surface expression of HLA-E mo...

Background: Platelet adhesion typically occurs by the critical role of GPIb-V-IX in capturing free-flowing platelets to the injured vessel wall where its rapid binding kinetics enables platelet tethering even under conditions of high shear through the interaction of the major ligand-binding subunit of GPIb-V-IX, GPIbα with subendothelial-bound vWF....

The expression levels of platelet receptors GPIba and P-selectin in response to different agonists and apoptosis inducer during the storage of platelet concentrates Mehran Ghasemzadeh, Ehteramolsadat Hosseini Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Introduction: GPIbα plays...

NCRs reconstitution supports functional recovery of NK cells following HLA-matched allogeneic hematopoietic stem cell transplantation Ehteramolsadat Hosseini, Mehran Ghasemzadeh Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Introduction: Graft-versus-leukemia (GvL) is often cruc...

Background: Major platelet adhesive receptors that contribute significantly to thrombus formation include platelet receptor glycoprotein Ibα (GPIbα) of the GPIb-IX-V complex and platelet glycoprotein VI (GPVI). GPIbα plays a crucial role in platelet tethering to sub-endothelial matrix, which initiates thrombus formation at arterial shear rates, whe...

NK cell-cytotoxicity against residual leukemic cells is crucial for immune system reconstitution after hematopoietic stem cell transplantation (HSCT). Since immune recovery after transplant still remains a major concern, we studied the counterbalance of NK cell receptors after HSCT and its importance in NK cell functional recovery. We investigated...

Background: Natural killer (NK) cells are members of the innate immune system. Their unique properties, including recognition of viral infected and tumor cells without major histocompatibility complex (MHC) restriction or prior sensitization, make them a suitable choice for immunotherapy. Low numbers of NK cells in circulating blood is the most imp...

Resistance to cell death and reprogramming of metabolism are important in neoplastic cells. Increased resistance to apoptosis and recurrence of tumors are the major roadblocks to effective treatment of triple negative breast cancer. It has been thought that execution of necroptosis involves ROS generation and mitochondrial dysfunction in malignant...

Background and purpose: Platelet concentrates (PCs) are used in treatment of quantitative and qualitative platelet defects. In some cases it can cause complications in recipients. In PC, white blood cells, some mediators, cytokines and microparticles can contribute to adverse reactions in recipients. In this study, the effects of platelet-derived m...

Abstract Thrombin is a central regulator of leukocyte recruitment and inflammation at sites of vascular injury, a function thought to involve primarily endothelial PAR cleavage. Here we demonstrate the existence of a distinct leukocyte-trafficking mechanism regulated by components of the haemostatic system, including platelet PAR4, GPIbα and fibrin...

Leukocytes recruitment to thrombi supports an intimate cellular interaction leading to the enhancement of pro-coagulant functions and pro-inflammatory responses at site of vascular injury. Recent observations of leukocytes neutrophil extracellular traps (NETs) formation and its mutual reactions with platelet thrombi adds more clinical interest to t...

Hematopoietic stem cell transplantation (HSCT) is complicated by histocompatibility dependent immune responses such as graft-versus-host disease (GvHD), relapse and graft rejection. The severity of these common adverse effects is directly related to the degree of HLA incompatibility. In addition to the key role of classic HLA matching in influencin...

Intraplatelet phospho-VASP analysis is a commonly used approach for monitoring of anti-platelet therapy; however, testing of intraplatelet phospho-VASP expression needs a high level of experience and proficiency. The ability to recognize how the pre-analytical variations can change the results would be helpful for the interpretation of data from in...

Background: Ischemia-reperfusion injury is associated with an intense inflammatory infiltrate that exacerbates tissue injury. It is generally considered that ischemic injury to the endothelium, leading to upregulated expression of adhesion molecules and proinflammatory cytokines, is the principal mechanism promoting leukocyte recruitment and inflam...

Thrombosis promotes leukocyte infiltration into inflamed tissues, leading to organ injury in a broad range of diseases; however, the mechanisms by which thrombi guide leukocytes to sites of vascular injury remain ill-defined. Using mouse models of endothelial injury (traumatic or ischemia reperfusion), we demonstrate a distinct process of leukocyte...

Abstract Purpose: This study has been conducted to evaluate the effect of urea on aggregation responses of heat-treated platelets. Materials and methods: The urea was added to platelet-rich plasma (PRP) samples in final concentrations of 50 and 100 mM. PRP samples, with or without exogenous urea, were incubated at 37 °C, 39 °C and 41 °C for 90 min...

Aim Thrombosis stimulates inflammation, leading to organ injury in a broad range of human diseases, however, the mechanisms regulating this phenomenon remains ill-defined. We therefore sought to define the mechanism by which microvascular thrombi guide leukocytes to sites of vascular injury. Results We developed an ischemia reperfusion (I/R) injury...

Platelet activation and adhesion to the site of vascular injury is a dynamic process comprising reversible and irreversible phases. Platelet adhesion typically occurs in a multi-step process similar to the selectin/integrin-mediated adhesion of neutrophils. This phenomenon is highly regulated and influenced by the cross-talk between platelets and i...

The non-classical MHC class-I mainly involves in the regulation of innate immune responses where HLA-E plays a significant role in the cell identification by natural killer cells. HLA-E is a main regulatory ligand for natural killer cells and given the importance of these effector cells in hematopoietic stem cell transplantation, we investigated th...

Platelet activation and adhesion to the site of vascular injury is a dynamic process comprising reversible and irreversible phases. Platelet adhesion typically occurs in a multi-step process similar to the selectin/integrin-mediated adhesion of neutrophils. This phenomenon is highly regulated and influenced by the cross-talk between platelets and i...

The formation of thrombi throughout the microvasculature of vital organs is a serious complication of a variety of systemic disorders, including disseminated intravascular coagulation and the thrombotic microangiopathies. Microvascular thrombi promote organ damage by obstructing blood flow and promoting a proinflammatory response, however it is unc...

The recruitment of leukocytes to sites of infection or inflammation is dependent on a unidirectional multi-step adhesion mechanism with the surface of endothelial cells or through ‘secondary capture’ by endothelial-bound platelets. Platelet thrombi are also efficient at capturing leukocytes from flowing blood and promoting leukocyte infiltration in...

Chronic renal failure is one of the causes of euthyroidism which is associated with some abnormalities in thyroid hormone metabolism. Although dialysis does not significantly affect these abnormalities, but renal transplantation leads to improve the conditions. In this study, first serum levels of thyrotropin and thyroid hormones and triiodothyroni...