Signaling Pathways of Receptors Involved in Platelet Activation andShedding of These Receptors in Stored Platelets

All cells encounter various signals coming from the surrounding environment and they need toreceive and respond to these signals in order to perform their functions. Cell surface receptorsare responsible for signal transduction .Platelets are blood cells which perform several functionsusing diverse receptors. Platelet concentrate is one of the most consumed blood products.However, due to the short lifespan of the platelets and platelets damage during storage, we faceshortage of platelet products. One of the damages that platelets undergo during storage is theloss of surface receptors. Since cell surface receptors are responsible for all cell functions, theloss of platelet receptors reduces the quality of platelet products. In this study, we reviewed theimportant receptors involved in platelet activation and their associated signaling pathways. Wealso looked at the platelet receptors that shed during storage and the causes of this incident.We found that GPIbα, P-selectin, CD40 and GPVI are platelet receptors that fall during plateletstorage at room temperature. Considering that GPVI and GPIbα are the most important receptorswhich involved in platelet activation, their shedding can cause decrease in platelet activationafter transfusion and decrease thrombus consistence. Shear stress and platelet contact with thecontainer wall are among the mechanisms discussed in this process, but studies in this area haveto be continued

Effects of Mesenchymal Stem Cell Derivatives on Hematopoiesis and Hematopoietic Stem Cells

Hematopoiesis is a balance among quiescence, self-renewal, proliferation, and differentiation, which is believed to be firmly adjusted through interactions between hematopoietic stem and progenitor cells (HSPCs) with the microenvironment. This microenvironment is derived from a common progenitor of mesenchymal origin and its signals should be capable of regulating the cellular memory of transcriptional situation and lead to an exchange of stem cell genes expression. Mesenchymal stem cells (MSCs) have self-renewal and differentiation capacity into tissues of mesodermal origin, and these cells can support hematopoiesis through release various molecules that play a crucial role in migration, homing, self-renewal, proliferation, and differentiation of HSPCs. Studies on the effects of MSCs on HSPC differentiation can develop modern solutions in the treatment of patients with hematologic disorders for more effective Bone Marrow (BM) transplantation in the near future. However, considerable challenges remain on realization of how paracrine mechanisms of MSCs act on the target tissues, and how to design a therapeutic regimen with various paracrine factors in order to achieve optimal results for tissue conservation and regeneration. The aim of this review is to characterize and consider the related aspects of the ability of MSCs secretome in protection of hematopoiesis

The Effect of Mesenchymal Stem Cell-Derived Microvesicles on Erythroid Differentiation of Umbilical Cord Blood-Derived CD34+ Cells

Purpose: Mesenchymal stem cells (MSCs) play an important role in the proliferation and differentiation of hematopoietic stem cells (HSCs) in the bone marrow via cell-to-cell contact, as well as secretion of cytokines and microvesicles (MVs). In this study, we investigated the effect of mesenchymal stem cell-derived microvesicles (MSC-MVs) on erythroid differentiation of umbilical cord blood-derived CD34+ cells. Methods: In this descriptive study, CD34+ cells were cultured with mixture of SCF (10 ng/ml) and rhEPO (5 U/ml) cytokines in complete IMDM medium as positive control group. Then, in MV1- and MV2-groups, microvesicles at 10 and 20 µg/ml concentration were added. After 72 hours, erythroid specific markers (CD71 and CD235a) and genes (HBG1, GATA1, FOG1 and NFE2) were assessed by flow cytometry and qRT-PCR, respectively. Results: The expression of specific markers of the erythroid lineages (CD71 and GPA) in the presence of different concentration of microvesicles were lower than that of the control group (P<0.001). Also, the expression of specific genes of the erythroid lineages (NFE2, FOG1, GATA1, and HBG1) was investigated in comparison to the internal control (GAPDH). Among all of them, HBG1 and FOG1 genes were significantly decreased to the control group (P<0.0001) but GATA1 and NFE2 gene expressions was not significant. Conclusion: The results of this study showed that MSC-MVs decrease the erythroid differentiation of umbilical cord blood-derived CD34+ cells. Therefore, MSC-MVs play a key role in the regulation of normal erythropoiesis

Mesenchymal stromal cells’ therapy for polyglutamine disorders: where do we stand and where should we go?

Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by the expansion of the cytosine-adenine-guanine (CAG) repeat. This mutation encodes extended glutamine (Q) tract in the disease protein, resulting in the alteration of its conformation/physiological role and in the formation of toxic fragments/aggregates of the protein. This group of heterogeneous disorders shares common molecular mechanisms, which opens the possibility to develop a pan therapeutic approach. Vast efforts have been made to develop strategies to alleviate disease symptoms. Nonetheless, there is still no therapy that can cure or effectively delay disease progression of any of these disorders. Mesenchymal stromal cells (MSC) are promising tools for the treatment of polyQ disorders, promoting protection, tissue regeneration, and/or modulation of the immune system in animal models. Accordingly, data collected from clinical trials have so far demonstrated that transplantation of MSC is safe and delays the progression of some polyQ disorders for some time. However, to achieve sustained phenotypic amelioration in clinics, several treatments may be necessary. Therefore, efforts to develop new strategies to improve MSC's therapeutic outcomes have been emerging. In this review article, we discuss the current treatments and strategies used to reduce polyQ symptoms and major pre-clinical and clinical achievements obtained with MSC transplantation as well as remaining flaws that need to be overcome. The requirement to cross the blood-brain-barrier (BBB), together with a short rate of cell engraftment in the lesioned area and low survival of MSC in a pathophysiological context upon transplantation may contribute to the transient therapeutic effects. We also review methods like pre-conditioning or genetic engineering of MSC that can be used to increase MSC survival in vivo, cellular-free approaches-i.e., MSC-conditioned medium (CM) or MSC-derived extracellular vesicles (EVs) as a way of possibly replacing the use of MSC and methods required to standardize the potential of MSC/MSC-derived products. These are fundamental questions that need to be addressed to obtain maximum MSC performance in polyQ diseases and therefore increase clinical benefits.Portuguese Foundation for Science and Technology: SFRH/BD/148877/2019; CENTRO01-0145-FEDER-000008 CENTRO-01-0145FEDER-022095 POCI-01-0145-FEDER-016719 POCI-01-0145-FEDER-029716 POCI01-0145-FEDER-016807 POCI-01-0145-FEDER016390 UID4950/2020 CENTRO-01-0145-FEDER-022118info:eu-repo/semantics/publishedVersio

Mesenchymal Stem Cell - Derived Exosomes: New Opportunity i n Cell - Free Therapy

Mesenchymal stromal/stem cells (MSCs) are involved in tissue homeostasis through direct cell - to - cell interaction, as well as secretion of soluble factors. Exosomes are the sort of soluble biological mediators that obtained from MSCs cultured media in vitro. MSC - deriv ed exosomes ( MSC - DEs ) which produced under physiological or pathological conditions are central mediators of intercellular communications by conveying proteins, lipids, mRNAs, siRNA, ribosomal RNAs and miRNAs to the neighbor or distant cells. MSC - DEs have been tested in various disease models, and the results have revealed that their functions are similar to those of MSCs. They have the supportive functions in organisms such as repairing tissue damages, suppressing inflammatory responses, and modulating the immune system. MSC - DEs are of great interest in the scope of regenerative medicine because of their unique capacity to the regeneration of the damaged tissues , and the present paper aims to introduce MSC - DEs as a novel hope in cell - free therapy

The Effect of Mesenchymal Stem Cell-Derived Extracellular Vesicles on Hematopoietic Stem Cells Fate

Hematopoietic stem cells (HSCs) are multipotent stem cells, with self-renewal ability as well as ability to generate all blood cells. Mesenchymal stem cells (MSCs) are multipotent stem cells, with self-renewal ability, and capable of differentiating into a variety of cell types. MSCs have supporting effects on hematopoiesis; through direct intercellular communications as well as secreting cytokines, chemokines, and extracellular vesicles (EVs). Recent investigations demonstrated that some biological functions and effects of MSCs are mediated by their EVs. MSC-EVs are the cell membrane and endosomal membrane compartments, which are important mediators in the intercellular communications. MSC-EVs contain some of the molecules such as proteins, mRNA, siRNA, and miRNA from their parental cells. MSC-EVs are able to inhibit tumor, repair damaged tissue, and modulate immune system responses. MSC-EVs compared to their parental cells, may have the specific safety advantages such as the lower potential to trigger immune system responses and limited side effects. Recently some studies demonstrated the effect of MSC-EVs on the expansion, differentiation, and clinical applications of HSCs such as improvement of hematopoietic stem cell transplantation (HSCT) and inhibition of graft versus host disease (GVHD). HSCT may be the only therapeutic choice for patients who suffer from malignant and non-malignant hematological disorders. However, there are several severe side effects such GVHD that restricts the successfulness of HSCT. In this review, we will discuss the most important effects of MSCs and MSC-EVs on the improvement of HSCT, inhibition and treatment of GVHD, as well as, on the expansion of HSCs