scholarly journals Mesenchymal stromal cells can be applied to red blood cells storage as a kind of cellular additive

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Yaozhen Chen ◽  
Jing Zhang ◽  
Shunli Gu ◽  
Dandan Yin ◽  
Qunxing An ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Blood Cells ◽  
Storage Duration ◽  
Hematopoietic Stem ◽  
Diminished Capacity ◽  
Blood Banks ◽  
Citrate Phosphate

During storage in blood banks, red blood cells (RBCs) undergo the mechanical and metabolic damage, which may lead to the diminished capacity to deliver oxygen. At high altitude regions, the above-mentioned damage may get worse. Thus, more attention should be paid to preserve RBCs when these components need transfer from plain to plateau regions. Recently, we found that mesenchymal stromal cells (MSCs) could rescue from anemia, and MSCs have been demonstrated in hematopoietic stem cells (HSCs) transplantation to reconstitute hematopoiesis in vivo by us. Considering the functions and advantages of MSCs mentioned above, we are trying to find out whether they are helpful to RBCs in storage duration at high altitudes. In the present study, we first found that mice MSCs could be preserved in citrate phosphate dextrose adenine-1 (CPDA-1) at 4 ± 2°C for 14 days, and still maintained great viability, even at plateau region. Thus, we attempted to use MSCs as an available supplement to decrease RBCs lesion during storage. We found that MSCs were helpful to support RBCs to maintain biochemical parameters and kept RBCs function well on relieving anemia in an acute hemolytic murine model. Therefore, our investigation developed a method to get a better storage of RBCs through adding MSCs, which may be applied in RBCs storage as a kind of cellular additive into preservation solution.

scholarly journals In VitroLarge Scale Production of Human Mature Red Blood Cells from Hematopoietic Stem Cells by Coculturing with Human Fetal Liver Stromal Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jiafei Xi ◽  
Yanhua Li ◽  
Ruoyong Wang ◽  
Yunfang Wang ◽  
Xue Nan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cord Blood ◽  
Red Blood Cells ◽  
Stromal Cells ◽  
Blood Cells ◽  
Fetal Liver ◽  
Erythroid Differentiation ◽  
Erythroid Cells ◽  
Hematopoietic Stem

In vitromodels of human erythropoiesis are useful in studying the mechanisms of erythroid differentiation in normal and pathological conditions. Here we describe an erythroid liquid culture system starting from cord blood derived hematopoietic stem cells (HSCs). HSCs were cultured for more than 50 days in erythroid differentiation conditions and resulted in a more than 109-fold expansion within 50 days under optimal conditions. Homogeneous erythroid cells were characterized by cell morphology, flow cytometry, and hematopoietic colony assays. Furthermore, terminal erythroid maturation was improved by cosculturing with human fetal liver stromal cells. Cocultured erythroid cells underwent multiple maturation events, including decrease in size, increase in glycophorin A expression, and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to 80% of the cells. Importantly, they possessed the capacity to express the adult definitiveβ-globin chain upon further maturation. We also show that the oxygen equilibrium curves of the cord blood-differentiated red blood cells (RBCs) are comparable to normal RBCs. The large number and purity of erythroid cells and RBCs produced from cord blood make this method useful for fundamental research in erythroid development, and they also provide a basis for future production of available RBCs for transfusion.

scholarly journals Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells

Science ◽  
2021 ◽  
Vol 371 (6533) ◽  
pp. 1019-1025
Author(s):  
Yuanbin Song ◽  
Liang Shan ◽  
Rana Gbyli ◽  
Wei Liu ◽  
Till Strowig ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Bone Marrow Failure ◽  
Complement C3 ◽  
In Vivo Models ◽  
Hematopoietic Stem ◽  
Human Red Blood Cells ◽  
Fumarylacetoacetate Hydrolase ◽  
Intrasplenic Injection

In vivo models that recapitulate human erythropoiesis with persistence of circulating red blood cells (RBCs) have remained elusive. We report an immunodeficient murine model in which combined human liver and cytokine humanization confer enhanced human erythropoiesis and RBC survival in the circulation. We deleted the fumarylacetoacetate hydrolase (Fah) gene in MISTRG mice expressing several human cytokines in place of their murine counterparts. Liver humanization by intrasplenic injection of human hepatocytes (huHep) eliminated murine complement C3 and reduced murine Kupffer cell density. Engraftment of human sickle cell disease (SCD)–derived hematopoietic stem cells in huHepMISTRGFah−/− mice resulted in vaso-occlusion that replicated acute SCD pathology. Combined liver–cytokine–humanized mice will facilitate the study of diseases afflicting RBCs, including bone marrow failure, hemoglobinopathies, and malaria, and also preclinical testing of therapies.

Human Multipotent Mesenchymal Stromal Cells Inhibit Proliferation of PBMC in the Absence of Functional IFNγR1 and IDO Expression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2567-2567
Author(s):  
Friederike Gieseke ◽  
Susanne Viebahn ◽  
Sandra Kordowich ◽  
Ewa Koscielniak ◽  
Wilhelm Friedrich ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Molecular Mechanism ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Interferon Γ ◽  
Hematopoietic Stem ◽  
Indoleamine 2,3 Dioxygenase

Abstract Human multipotent mesenchymal stromal cells (MSC) can easily be isolated and propagated from bone marrow. MSC have been shown to inhibit the proliferation and effector functions of immune cells such as T cells, B cells, NK cells and dendritic cells. Over the recent years, they have gained clinical interest in transplantation and regenerative medicine. In allogeneic stem cell transplantation, MSC have been clinically applied not only because of their stromal support for hematopoietic stem cells, but also because of their immunomodulatory effects in graft-versus-host disease (GvHD). However, the molecular mechanism is not fully understood yet. In several studies the enzyme indoleamine 2,3-dioxygenase (IDO) has been described as a candidate be involved in this molecular mechanism. IDO has been shown to suppress T cell responses when expressed in dendritic cells by degradation of the essential amino acid tryptophan. In vivo, IDO is important to induce and maintain tolerance for the fetus during pregnancy. Although IDO is not expressed in MSC constitutively, it can strongly be induced by interferon-γ (IFNγ). Contradictory results have been published regarding the role of IFNγ-induced IDO expression in immunomodulation by MSC and it is still a matter of debate whether IDO is required in this setting. To clarify this contentious issue we carried out proliferation assays with PBMC stimulated by IL-2 and OKT-3 either in the presence or absence of HLA-mismatched MSC. We added exogenous IFNγ in order to induce IDO, which should have enhanced the inhibition of PBMC proliferation mediated by MSC. However, the effect of MSC was similar in cultures with or without exogenous IFNγ. Neither did pre-incubation of MSC with IFNγ before adding PBMC and IL-2 and OKT-3 have any effect on the inhibition. Moreover, we analyzed the effect of the IDO inhibitor 1-methyl-tryptophan. By adding 1-methyl-tryptophan the proliferation of PBMC in the presence of MSC could not be restored. These results suggested that expression of IDO in MSC was not responsible for the inhibition of PBMC. To further rule out that IFNγ produced by PBMC was sufficient to induce IDO and inhibition by 1-methyl-tryptophan was not complete, we isolated MSC from bone marrow of a child with a mutation in the subunit I of the INFγ receptor (IFNγR1) leading to a non-functional IFNg receptor. MSCIFNγR1−/− behaved normal in terms of plasticity and were readily differentiated into osteoblasts and adipocytes by standard protocols. Interestingly, MSCIFNγR1−/− were able to suppress the proliferation of PBMC to the same extent as MSC with functional IFNγ receptor. This showed that MSC inhibit PBMC independent of functional IFNγR1. Subsequently, we analyzed IDO expression in MSCIFNγR1−/− by RT-PCR. Expectedly, we could show that in MSCIFNγR1−/− IDO was neither expressed constitutively nor was it induced by incubation with IFNγ. Taken together, these findings conclusively demonstrate that neither IFNγR1-mediated effects of IFNγ nor indoleamine 2,3-dioxygenase are involved in the molecular mechanism used by MSC to inhibit PBMC proliferation.

scholarly journals Nuclear shape, protrusive behaviour and in vivo retention of human bone marrow mesenchymal stromal cells is controlled by Lamin-A/C expression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yvonne L. Dorland ◽  
Anne S. Cornelissen ◽  
Carlijn Kuijk ◽  
Simon Tol ◽  
Mark Hoogenboezem ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Nuclear Lamina ◽  
Cell Types ◽  
Lamin A ◽  
Human Mscs ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Abstract Culture expanded mesenchymal stromal cells (MSCs) are being extensively studied for therapeutic applications, including treatment of graft-versus-host disease, osteogenesis imperfecta and for enhancing engraftment of hematopoietic stem cells after transplantation. Thus far, clinical trials have shown that the therapeutic efficiency of MSCs is variable, which may in part be due to inefficient cell migration. Here we demonstrate that human MSCs display remarkable low migratory behaviour compared to other mesodermal-derived primary human cell types. We reveal that specifically in MSCs the nucleus is irregularly shaped and nuclear lamina are prone to wrinkling. In addition, we show that expression of Lamin A/C is relatively high in MSCs. We further demonstrate that in vitro MSC migration through confined pores is limited by their nuclei, a property that might correlate to the therapeutic inefficiency of administered MSC in vivo. Silencing expression of Lamin A/C in MSCs improves nuclear envelope morphology, promotes the protrusive activity of MSCs through confined pores and enhances their retention in the lung after intravenous administration in vivo. Our findings suggest that the intrinsic nuclear lamina properties of MSCs underlie their limited capacity to migrate, and that strategies that target the nuclear lamina might alter MSC-based cellular therapies.

scholarly journals What makes our lungs look red?

2021 ◽  
Author(s):  
Song Huang ◽  
Cindia Lopez
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Cell Types ◽  
Red Cells ◽  
Human Beings ◽  
Hematopoietic Stem ◽  
Therapeutic Implications ◽  
Dense Networks ◽  
Different Cell Types

What makes our lungs look red? This seems to be a naive and trivial question. Indeed, all the textbooks tell us that what makes our body red is the presence of blood, or more precisely the red blood cells (RBC). Here we provide some experimental evidence as well arguments to prove that this belief is wrong, or only partially true. In fact, we identified an important population of red cells located outside of the blood vessels as highly compacted clusters, in the connection tissues of the lungs of several species of animals including rats and human beings. These red cells possessed each a nucleus, expressing several biomarkers of different cell types such as PF4, vWF, SCF-1R, CD200R, TGF-b, etc. Interestingly, being morphologically heterogeneous, they react collectively to certain stimuli. For example, they aggregated on collagen fibers forming clusters of cells resembling that observed in vivo. The red cells may have some features of Hematopoietic Stem Cells since they were capable of differentiating into other cell types such as alveolar macrophages. In nasal polyps, these cells formed vessel-like structures, confined within a CD31-positive tube. Upon exposure to toxic chemicals, they formed dense networks, suggesting a possible role in coagulation. Furthermore, the number of these red cells was greatly increased in the lungs of deceased donors, especially in the lungs of CF patients. Instead of being secreted as what happens in normal red cells, vWF proteins were tethered on the cytoplasmic membrane of the red cells isolated from the lungs of CF donors, which may explain at least partially the fibrotic nature of the CF lungs. Taken together, we conclude that what makes the lungs look red is not the red blood cells, rather a distinct population of red cells, we call them Red Soma Cells (RSC). We believe that the discovery and characterization of this important population of cells will have profound theoretical as well as therapeutic implications.

scholarly journals Mesenchymal stromal cells in hematopoietic cell transplantation

2020 ◽  
Vol 4 (22) ◽  
pp. 5877-5887
Author(s):  
Andre J. Burnham ◽  
Lisa P. Daley-Bauer ◽  
Edwin M. Horwitz
Keyword(s):  
Cell Transplantation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Hematopoietic Cell Transplantation ◽  
The United States ◽  
Hematopoietic Cell ◽  
Immunomodulatory Activity ◽  
Critical Determinant ◽  
Hematopoietic Stem

Abstract Mesenchymal stromal cells (MSCs) are widely recognized to possess potent immunomodulatory activity, as well as to stimulate repair and regeneration of diseased or damaged tissue. These fundamental properties suggest important applications in hematopoietic cell transplantation. Although the mechanisms of therapeutic activity in vivo are yet to be fully elucidated, MSCs seem to suppress lymphocytes by paracrine mechanisms, including secreted mediators and metabolic modulators. Most recently, host macrophage engulfment of apoptotic MSCs has emerged as an important contributor to the immune suppressive microenvironment. Although bone marrow–derived MSCs are the most commonly studied, the tissue source of MSCs may be a critical determinant of immunomodulatory function. The key application of MSC therapy in hematopoietic cell transplantation is to prevent or treat graft-versus-host disease (GVHD). The pathogenesis of GVHD reveals multiple potential targets. Moreover, the recently proposed concept of tissue tolerance suggests a new possible mechanism of MSC therapy for GVHD. Beyond GVHD, MSCs may facilitate hematopoietic stem cell engraftment, which could gain greater importance with increasing use of haploidentical transplantation. Despite many challenges and much doubt, commercial MSC products for pediatric steroid-refractory GVHD have been licensed in Japan, conditionally licensed in Canada and New Zealand, and have been recommended for approval by an FDA Advisory Committee in the United States. Here, we review key historical data in the context of the most salient recent findings to present the current state of MSCs as adjunct cell therapy in hematopoietic cell transplantation.

scholarly journals Tolerance to Bone Marrow Transplantation: Do Mesenchymal Stromal Cells Still Have a Future for Acute or Chronic GvHD?

2020 ◽  
Vol 11 ◽  
Author(s):  
Martino Introna ◽  
Josée Golay
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Pathological Condition ◽  
Statistical Significance ◽  
Chronic Gvhd ◽  
Differentiation Potential ◽  
Hematopoietic Stem

Mesenchymal Stromal Cells (MSCs) are fibroblast-like cells of mesodermal origin present in many tissues and which have the potential to differentiate to osteoblasts, adipocytes and chondroblasts. They also have a clear immunosuppressive and tissue regeneration potential. Indeed, the initial classification of MSCs as pluripotent stem cells, has turned into their identification as stromal progenitors. Due to the relatively simple procedures available to expand in vitro large numbers of GMP grade MSCs from a variety of different tissues, many clinical trials have tested their therapeutic potential in vivo. One pathological condition where MSCs have been quite extensively tested is steroid resistant (SR) graft versus host disease (GvHD), a devastating condition that may occur in acute or chronic form following allogeneic hematopoietic stem cell transplantation. The clinical and experimental results obtained have outlined a possible efficacy of MSCs, but unfortunately statistical significance in clinical studies has only rarely been reached and effects have been relatively limited in most cases. Nonetheless, the extremely complex pathogenetic mechanisms at the basis of GvHD, the fact that studies have been conducted often in patients who had been previously treated with multiple lines of therapy, the variable MSC doses and schedules administered in different trials, the lack of validated potency assays and clear biomarkers, the difference in MSC sources and production methods may have been major factors for this lack of clear efficacy in vivo. The heterogeneity of MSCs and their different stromal differentiation potential and biological activity may be better understood through more refined single cell sequencing and proteomic studies, where either an “anti-inflammatory” or a more “immunosuppressive” profile can be identified. We summarize the pathogenic mechanisms of acute and chronic GvHD and the role for MSCs. We suggest that systematic controlled clinical trials still need to be conducted in the most promising clinical settings, using better characterized cells and measuring efficacy with specific biomarkers, before strong conclusions can be drawn about the therapeutic potential of these cells in this context. The same analysis should be applied to other inflammatory, immune or degenerative diseases where MSCs may have a therapeutic potential.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

The Ullrastructure of Platelet Participation in Hemostasis

1965 ◽  
Vol 13 (01) ◽  
pp. 065-083 ◽  
Author(s):  
Shirley A. Johnson ◽  
Ronaldo S. Balboa ◽  
Harlan J. Pederson ◽  
Monica Buckley
Keyword(s):  
Platelet Aggregation ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Guinea Pigs ◽  
Platelet Factor ◽  
Mesenteric Vessels ◽  
Platelet Aggregates ◽  
Electron Lucent

SummaryThe ultrastructure of platelet aggregation in vivo in response to bleeding brought about by transection of small mesenteric vessels in rats and guinea pigs has been studied. Platelets aggregate, degranulate and separating membranes disappear in parallel with fibrin appearance which is first seen at several loci after 30 seconds of bleeding. About 40 per cent of the electron opaque granules, some of which contain platelet factor 3 have disappeared after one minute of bleeding while the electron lucent granules increase by 70 per cent suggesting that some of them may be empty vesicles. Most of the platelet aggregates of the random type disappear leaving clumped red blood cells entrapped by a network of fibrin fibers which emanate from the remains of platelet aggregates of the rosette type to maintain hemostasis.

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