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1.
Di Giacomo F Lewandowski D Cabannes E Nancy-Portebois V Petitou M Fichelson S Romeo PH 《Haematologica》2012,97(4):491-499
Background
Although mobilization of hematopoietic stem cells and hematopoietic progenitor cells can be achieved with a combination of granulocyte colony-stimulating factor and plerixafor (AMD3100), improving approaches for hematopoietic progenitor cell mobilization is clinically important.Design and Methods
Heparan sulfate proteoglycans are ubiquitous macromolecules associated with the extracellular matrix that regulates biology of hematopoietic stem cells. We studied the effects of a new family of synthetic oligosaccharides mimicking heparan sulfate on hematopoietic stem cell mobilization. These oligosaccharides were administered intravenously alone or in combination with granulocyte colony-stimulating factor and/or AMD3100 in mice. Mobilized hematopoietic cells were counted and phenotyped at different times and the ability of mobilized hematopoietic stem cells to reconstitute long-term hematopoiesis was determined by competitive transplantation into syngenic lethally irradiated mice followed by secondary transplantation.Results
Mimetics of heparan sulfate induced rapid mobilization of B-lymphocytes, T-lymphocytes, hematopoietic stem cells and hematopoietic progenitor cells. They increased the mobilization of hematopoietic stem cells and hematopoietic progenitor cells more than 3-fold when added to the granulocyte colony-stimulating factor/AMD3100 association. Hematopoietic stem cells mobilized by mimetics of heparan sulfate or by the granulocyte colony-stimulating factor/AMD3100/mimetics association were as effective as hematopoietic stem cells mobilized by the granulocyte colony-stimulating factor/AMD3100 association for primary and secondary hematopoietic reconstitution of lethally irradiated mice.Conclusions
This new family of mobilizing agents could alone or in combination with granulocyte colony-stimulating factor and/or AMD3100 mobilize a high number of hematopoietic stem cells that were able to maintain long-term hematopoiesis. These results strengthen the role of heparan sulfates in the retention of hematopoietic stem cells in bone marrow and support the use of small glyco-drugs based on heparan sulfate in combination with granulocyte colony-stimulating factor and AMD3100 to improve high stem cell mobilization, particularly in a prospect of use in human therapeutics. 相似文献2.
Nicole D. Staudt Wilhelm K. Aicher Hubert Kalbacher Stefan Stevanovic Adriana K. Carmona Matthew Bogyo Gerd Klein 《Haematologica》2010,95(9):1452-1460
Background
Hematopoietic stem cells are retained within discrete bone marrow niches through the effects of cell adhesion molecules and chemokine gradients. However, a small proportion of hematopoietic stem cells can also be found trafficking in the peripheral blood. During induced stem cell mobilization a proteolytic microenvironment is generated, but whether proteases are also involved in physiological trafficking of hematopoietic stem cells is not known. In the present study we examined the expression, secretion and function of the cysteine protease cathepsin X by cells of the human bone marrow.Design and Methods
Human osteoblasts, bone marrow stromal cells and hematopoietic stem and progenitor cells were analyzed for the secretion of cathepsin X by western blotting, active site labeling, immunofluorescence staining and activity assays. A possible involvement of cathepsin X in cell adhesion and CXCL-12-mediated cell migration was studied in functional assays. Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) analysis revealed the digestion mechanism of CXCL-12 by cathepsin X.Results
Osteoblasts and stromal cells secrete cathepsin X, whereas hematopoietic stem and progenitor cells do not. Using a cathepsin X-selective substrate, we detected the catalytic activity of cathepsin X in cell culture supernatants of osteoblasts. Activated cathepsin X is able to reduce cellular adhesive interactions between CD34+ hematopoietic stem and progenitor cells and adherent osteoblasts. The chemokine CXCL-12, a highly potent chemoattractant for hematopoietic stem cells secreted by osteoblasts, is readily digested by cathepsin X.Conclusions
The exo-peptidase cathepsin X has been identified as a new member of the group of CXCL-12-degrading enzymes secreted by non-hematopoietic bone marrow cells. Functional data indicate that cathepsin X can influence hematopoietic stem and progenitor cell trafficking in the bone marrow. 相似文献3.
4.
Evert-Jan F.M. de Kruijf Henny Hagoort Gerjo A. Velders Willem E. Fibbe Melissa van Pel 《Haematologica》2010,95(7):1061-1067
Background
Flt3-ligand is a cytokine that induces relatively slow mobilization of hematopoietic cells in animals and humans in vivo. This provides a time-frame to study hematopoietic stem and progenitor cell migration kinetics in detail.Design and Methods
Mice were injected with Flt3-ligand (10 μg/day, intraperitoneally) for 3, 5, 7 and 10 days. Mobilization of hematopoietic stem and progenitor cells was studied using colony-forming-unit granulocyte/monocyte and cobblestone-area-forming-cell assays. The radioprotective capacity of mobilized peripheral blood mononuclear cells was studied by transplantation of 1.5×106 Flt3-ligand-mobilized peripheral blood mononuclear cells into lethally irradiated (9.5 Gy) recipients.Results
Hematopoietic progenitor cell mobilization was detected from day 3 onwards and prolonged administration of Flt3-ligand produced a steady increase in mobilized progenitor cells. Compared to Flt3-ligand administration for 5 days, the administration of Flt3-ligand for 10 days led to a 5.5-fold increase in cobblestone-area-forming cells at week 4 and a 5.0-fold increase at week 5. Furthermore, transplantation of peripheral blood mononuclear cells mobilized by 5 days of Flt3-ligand administration did not radioprotect lethally irradiated recipients, whereas peripheral blood mononuclear cells mobilized by 10 days of Flt3-Ligand administration did provide 100% radioprotection of the recipients with significant multilineage donor chimerism. Compared to the administration of Flt3-ligand or interleukin-8 alone, co-administration of interleukin-8 and Flt3-ligand led to synergistic enhancement of hematopoietic stem and progenitor cell mobilization on days 3 and 5.Conclusions
These results indicate that hematopoietic stem and progenitor cells show different mobilization kinetics in response to Flt3-ligand, resulting in preferential mobilization of hematopoietic progenitor cells at day 5, followed by hematopoietic stem cell mobilization at day 10. 相似文献5.
Background
In the bone marrow mesenchymal stromal cells and osteoblasts form functional niches for hematopoietic stem and progenitor cells. This microenvironment can be partially mimicked using in vitro co-culture systems. In this study, we examined the oxygen tension in three distinct compartments in a co-culture system of purified CD34+ cells and mesenchymal stromal cells with regard to different spatial localizations.Design and Methods
Hypoxic cells in the co-culture were visualized by pimonidazole staining. Hematopoietic cell distribution, and functional and phenotypic characteristics were analyzed by flow cytometry. The secretion of vascular endothelial growth factor and stromal-derived factor-1 by mesenchymal stromal cells in low oxygen co-cultures was determined by an enzyme-linked immunosorbent assay. The effect of co-culture medium on the hematopoietic cell migration potential was tested in a transwell assay.Results
In co-cultures under atmospheric oxygen tension, regions of low oxygen tension could be detected beneath the feeder layer in which a reservoir of phenotypically more primitive hematopoietic cells is located in vitro. In low oxygen co-culture, the adhesion of hematopoietic cells to the feeder layer was decreased, whereas hematopoietic cell transmigration beneath mesenchymal stromal cells was favored. Increased vascular endothelial growth factor-A secretion by mesenchymal stromal cells under low oxygen conditions, which increased the permeability of the monolayer, was responsible for this effect. Furthermore, vascular endothelial growth factor-A expression in low oxygen mesenchymal stromal cells was induced via hypoxia-inducible factor signaling. However, stromal cell-derived factor-1 secretion by mesenchymal stromal cells was down-regulated under low oxygen conditions in a hypoxia-inducible factor-independent manner.Conclusions
We demonstrate for the first time that differences in oxygen tension cause selective modification of hematopoietic cell and mesenchymal stromal cell interactions in a co-culture system, thus confirming that oxygen tension plays a critical role in the interaction between hematopoietic cells and the niche environment. 相似文献6.
Xiaoli Wang Hiroko Hisha Tomomi Mizokami Wenhao Cui Yunze Cui Aiping Shi Changye Song Satoshi Okazaki Qing Li Wei Feng Junko Kato Susumu Ikehara 《Haematologica》2010,95(6):884-891
Background
We previously established a mesenchymal stem cell line (FMS/PA6-P) from the bone marrow adherent cells of fetal mice. The cell line expresses a higher level of neural cell adhesion molecule and shows greater hematopoiesis-supporting capacity in mice than other murine stromal cell lines.Design and Methods
Since there is 94% homology between human and murine neural cell adhesion molecule, we examined whether FMS/PA6-P cells support human hematopoiesis and whether neural cell adhesion molecules expressed on FMS/PA6-P cells contribute greatly to the human hematopoiesis-supporting ability of the cell line.Results
When lineage-negative cord blood mononuclear cells were co-cultured on the FMS/PA6-P cells, a significantly greater hematopoietic stem cell-enriched population (CD34+CD38− cells) was obtained than in the culture without the FMS/PA6-P cells. Moreover, when lineage-negative cord blood mononuclear cells were cultured on FMS/PA6-P cells and transplanted into SCID mice, a significantly larger proportion of human CD45+ cells and CD34+CD38− cells were detected in the bone marrow of SCID mice than in the bone marrow of SCID mice that had received lineage-negative cord blood mononuclear cells cultured without FMS/PA6-P cells. Furthermore, we found that direct cell-to-cell contact between the lineage-negative cord blood mononuclear cells and the FMS/PA6-P cells was essential for the maximum expansion of the mononuclear cells. The addition of anti-mouse neural cell adhesion molecule antibody to the culture significantly inhibited their contact and the proliferation of lineage-negative cord blood mononuclear cells.Conclusions
These findings suggest that neural cell adhesion molecules expressed on FMS/PA6-P cells play a crucial role in the human hematopoiesis-supporting ability of the cell line. 相似文献7.
Hematopoietic stem and progenitor cells (HSPCs) are located in the bone marrow in close association with a highly organized 3-dimensional structure formed by stroma cells, referred to as the niche. Mobilization of HSPCs from bone marrow to peripheral blood in response to granulocyte colony-stimulating factor (G-CSF) requires de-adhesion of HSPCs from the niche. The influence of aging of HSPCs on cell-stroma interactions has not been determined in detail. Using a mouse model of G-CSF-induced mobilization, we demonstrated that the ability to mobilize hematopoietic stem cells is approximately 5-fold greater in aged mice. Competitive mobilization experiments confirmed that enhanced mobilization ability was intrinsic to the stem cell. Enhanced mobilization efficiency of primitive hematopoietic cells from aged mice correlated with reduced adhesion of hematopoietic progenitor cells to stroma and with elevated levels of GTP-bound Cdc42. These results might indicate that stroma-stem cell interactions are dynamic over a lifetime and result in physiologically relevant changes in the biology of primitive hematopoietic cells with age. 相似文献
8.
Alexandra Briquet Sophie Dubois Sandrine Bekaert Marie Dolhet Yves Beguin Andr�� Gothot 《Haematologica》2010,95(1):47-56
Background
Bone marrow mesenchymal stem cells support proliferation and differentiation of hematopoietic progenitor cells in vitro. Since these cells constitute a rare subset of bone marrow cells, mesenchymal stem cell preparations for clinical purposes require a preparative step of ex vivo multiplication. The aim of our study was to analyze the influence of culture duration on mesenchymal stem cell supportive activity.Design and Methods
Mesenchymal stem cells were expanded for up to ten passages. These cells and CD34+ cells were seeded in cytokine-free co-cultures after which the phenotype, clonogenic capacity and in vivo repopulating activity of harvested hematopoietic cells were assessed.Results
Early passage mesenchymal stem cells supported hematopoietic progenitor cell expansion and differentiation toward both B lymphoid and myeloid lineages. Late passage mesenchymal stem cells did not support hematopoietic progenitor cell and myeloid cell outgrowth but maintained B-cell supportive ability. In vitro maintenance of NOD/SCID mouse repopulating cells cultured for 1 week in contact with mesenchymal stem cells was effective until the fourth passage of the mesenchymal cells and declined thereafter. The levels of engraftment of CD34+ cells in NOD/SCID mice was higher when these cells were co-injected with early passage mesenchymal stem cells; however mesenchymal cells expanded beyond nine passages were ineffective in promoting CD34+ cell engraftment. Non-contact cultures indicated that mesenchymal stem cell supportive activity involved diffusible factors. Among these, interleukins 6 and 8 contributed to the supportive activity of early passage mesenchymal stem cells but not to those of late passage cells. The phenotype, as well as fat, bone and cartilage differentiation capacity, of mesenchymal stem cells did not change during their culture.Conclusions
Extended culture of mesenchymal stem cells alters the ability of these cells to support hematopoietic progenitor cells without causing concomitant changes in their phenotype or differentiation capacity. 相似文献9.
Joerg Halter Yoshihisa Kodera Alvaro Urbano Ispizua Hildegard T. Greinix Norbert Schmitz Genevi��ve Favre Helen Baldomero Dietger Niederwieser Jane F. Apperley Alois Gratwohl 《Haematologica》2009,94(1):94-101
Background
The risk for donors of allogeneic hematopoietic stem cells transplants is generally considered negligible. Scattered reports of severe complications and a recent controversy on hematopoietic malignancies after granulocyte colony-stimulating factor administration have challenged this opinion.Design and Methods
Three hundred and thirty-eight allogeneic transplant teams from 35 primarily European countries were asked to report numbers of fatalities, severe adverse events and hematologic malignancies occurring among their hematopoietic stem cell donors.Results
Two hundred and sixty-two of the 338 teams (77.5%) responded to a first survey (1993–2002) and 169 of the 262 responder teams (65%) to a second survey (2003–2005). They had performed a total of 51,024 first allogeneic hematopoietic stem cell transplantations, of which 27,770 were bone marrow and 23,254 peripheral blood. They observed five donor fatalities, one after a bone marrow donation and four after peripheral blood donation (incidence 0.98 per 10,000 donations; 95% CI 0.32–2.29), 37 severe adverse events (7.25/10,000; 95% CI 5.11–9.99), of which 12 in bone marrow donors (4.32/10,000; 95% CI 2.24–7.75) and 25 in peripheral blood donors (10.76/10,000; 95% CI 6.97–15.85; p<0.05) and 20 hematologic malignancies (3.92/10,000; 95% CI 2.39–6.05), of which 8 after donating bone marrow and 12 after donating peripheral blood stem cells. The observed incidence rate of hematologic malignancies did not exceed the expected incidence in an age- and sex-adjusted general population.Conclusions
Hematopoietic stem cell donation is associated with a small but definite risk of fatalities and serious adverse events. True incidences might be higher, due to potential underreporting by study design. A continuous, standardized donor follow-up is needed to define donor risk groups and to monitor intermediate and long-term sequelae. 相似文献10.
Tomomi Mizokami Hiroko Hisha Satoshi Okazaki Takashi Takaki Xiao-Li Wang Chang-Ye Song Qing Li Junko Kato Naoki Hosaka Muneo Inaba Hideharu Kanzaki Susumu Ikehara 《Haematologica》2009,94(5):618-628
Background
We previously found in a murine hematopoietic system that hematopoietic stem cells show high differentiation and proliferation capacity on bone marrow-derived mesenchymal stem cells/stromal cells (microenvironment) with “self” major histocompatibility complex (MHC).Design and Methods
We examined whether amnion-derived adherent cells have the characteristics of mesenchymal stem cells, and whether these adherent cells can support the proliferation of umbilical cord blood-derived lineage-negative and CD34-positive cells (Lin–CD34+ cells) obtained from the same fetus to a greater extent than those derived from other fetuses.Results
Culture-expanded amnion-derived adherent cells expressed mesenchymal stem cell markers and HLA-ABC molecules and could differentiate into osteoblasts, adipocytes and chondrocyte-like cells, indicating that the cells have the characteristics of mesenchymal stem cells. The Lin–CD34+ cells purified from the frozen umbilical cord blood were strongly positive for HLA-ABC, and contained a large number of hematopoietic stem cells. When the Lin–CD34+ cells were cultured on the autologous (MHC-matched) or MHC-mismatched amnion-derived adherent cells in short-term assays (hematopoietic stem cell-proliferation) and long-term culture-initiating cell assays, greater expansion of the Lin–CD34+ cells was observed in the MHC-matched combination than in MHC-mismatched combinations. The concentration of granulocyte-macrophage colony-stimulating factor in the culture supernatants of the long-term culture-initiating cell assays was significantly higher in the MHC-matched combination than in MHC-mismatched combinations.Conclusions
It is likely that a MHC restriction exists between hematopoietic stem cells and mesenchymal stem cells/stromal cells in the human hematopoietic system and that granulocute-macropage colony-stimulating factor contributes to some extent to the preferential hematopoiesis-supporting ability of the MHC-matched amnion-derived adherent cells. 相似文献11.
Mueller RJ Stussi G Puga Yung G Nikolic M Soldini D Halter J Meyer-Monard S Gratwohl A Passweg JR Odermatt B Schanz U Biedermann BC Seebach JD 《Haematologica》2011,96(1):119-127
Background
The possibility that allogeneic hematopoietic stem cell transplantation performed across the ABO blood group-barrier is associated with an increase of graft-versus-host disease, in particular endothelial damage, has not been elucidated so far. For this reason, we investigated the level of endothelial cell chimerism after allogeneic hematopoietic stem cell transplantation in order to delineate the role of hematopoietic stem cells in endothelial replacement.Design and Methods
The frequency of donor-derived endothelial cells was analyzed in 52 hematopoietic stem cell transplant recipients, in 22 normal skin biopsies, in 12 skin samples affected by graft-versus-host disease, various tissues from five autopsies and four secondary solid tumors by ABH immunohistochemistry, XY fluorescence in situ hybridization and short tandem repeat analysis of laser captured endothelial cells.Results
Skin biopsies from two patients transplanted with minor ABO-incompatible grafts (i.e. O in A) showed 3.3% and 0.9% H antigen-positive donor-derived endothelial cells by ABH immunohistochemistry. Tumor biopsies from two recipients showed 1.2% and 2.5% donor-derived endothelial cells by combined immunohistochemistry/ fluorescence in situ hybridization. All other skin samples, heart, liver, bone-marrow, and tumor tissues failed to reveal donor-type endothelial cells up to several years after ABO-incompatible hematopoietic stem cell transplantation.Conclusions
Endothelial cell replacement by bone marrow-derived donor cells after allogeneic hematopoietic stem cell transplantation is a rare event. It does not seem to represent a major mechanism of physiological in vivo blood vessel formation, tumor neoangiogenesis, vascular repair after graft-versus-host disease episodes or acceptance of ABO-incompatible grafts. 相似文献12.
Maria Ximeri Athanasios Galanopoulos Mirjam Klaus Agapi Parcharidou Krinio Giannikou Maria Psyllaki Argyrios Symeonidis Vasiliki Pappa Zafiris Kartasis Dimitra Liapi Eleftheria Hatzimichael Styliani Kokoris Penelope Korkolopoulou Constantina Sambani Charalampos Pontikoglou Helen A. Papadaki 《Haematologica》2010,95(3):406-414
Background
Lenalidomide improves erythropoiesis in patients with low/intermediate-1 risk myelodysplastic syndrome and interstitial deletion of the long arm of chromosome 5 [del(5q)]. The aim of this study was to explore the effect of lenalidomide treatment on the reserves and functional characteristics of bone marrow hematopoietic progenitor/precursor cells, bone marrow stromal cells and peripheral blood lymphocytes in patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q).Design and Methods
We evaluated the number and clonogenic potential of bone marrow erythroid/myeloid/megakaryocytic progenitor cells using clonogenic assays, the apoptotic characteristics and adhesion molecule expression of CD34+ cells by flow cytometry, the hematopoiesis-supporting capacity of bone marrow stromal cells using long-term bone marrow cultures and the number and activation status of peripheral blood lymphocytes in ten patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q) receiving lenalidomide.Results
Compared to baseline, lenalidomide treatment significantly decreased the proportion of bone marrow CD34+ cells, increased the proportion of CD36+/GlycoA+ and CD36−/GlycoA+ erythroid cells and the percentage of apoptotic cells within these cell compartments. Treatment significantly improved the clonogenic potential of bone marrow erythroid, myeloid, megakaryocytic colony-forming cells and increased the proportion of CD34+ cells expressing the adhesion molecules CD11a, CD49d, CD54, CXCR4 and the SLAM antigen CD48. The hematopoiesis-supporting capacity of bone marrow stroma improved significantly following treatment, as demonstrated by the number of colony-forming cells and the level of stromal-derived factor-1α and intercellular adhesion molecule-1 in long-term bone marrow culture supernatants. Lenalidomide treatment also increased the proportion of activated peripheral blood T lymphocytes.Conclusions
The beneficial effect of lenalidomide in patients with lower risk myelodysplastic syndrome with del(5q) is associated with significant increases in the proportion of bone marrow erythroid precursor cells and in the frequency of clonogenic progenitor cells, a substantial improvement in the hematopoiesis-supporting potential of bone marrow stroma and significant alterations in the adhesion profile of bone marrow CD34+ cells. 相似文献13.
Background
A culture system that closely recapitulates marrow physiology is essential to study the niche-mediated regulation of hematopoietic stem cell fate at a molecular level. We investigated the key features that play a crucial role in the formation of a functional niche in vitro.Design and Methods
Hydrogel-based cultures of human placenta-derived mesenchymal stromal cells were established to recapitulate the fibrous three-dimensional architecture of the marrow. Plastic-adherent mesenchymal stromal cells were used as controls. Human bone marrow-derived CD34+ cells were co-cultured with them. The output hematopoietic cells were characterized by various stem cell-specific phenotypic and functional parameters.Results
The hydrogel-cultures harbored a large pool of primitive hematopoietic stem cells with superior phenotypic and functional attributes. Most importantly, like the situation in vivo, a significant fraction of these cells remained quiescent in the face of a robust multi-lineage hematopoiesis. The retention of a high percentage of primitive stem cells by the hydrogel-cultures was attributed to the presence of CXCR4-SDF1α axis and integrin beta1-mediated adhesive interactions. The hydrogel-grown mesenchymal stromal cells expressed high levels of several molecules that are known to support the maintenance of hematopoietic stem cells. Yet another physiologically relevant property exhibited by the hydrogel cultures was the formation of hypoxia-gradient. Destruction of hypoxia-gradient by incubating these cultures in a hypoxia chamber destroyed their specialized niche properties.Conclusions
Our data show that hydrogel-based cultures of mesenchymal stromal cells form a functional in vitro niche by mimicking key features of marrow physiology. 相似文献14.
15.
Anna Szmigielska-Kaplon Anna Krawczynska Magdalena Czemerska Agnieszka Pluta Barbara Cebula-Obrzut Katarzyna Szmigielska Konrad St?pka Piotr Smolewski Tadeusz Robak Agnieszka Wierzbowska 《Trasfusione del sangue》2015,13(1):102-108
Background
The bone marrow niche contains different types of cells including osteoblasts and endothelial progenitors, all of which interact and take part in the process of mobilisation. The aim of our study was to evaluate the levels of cytokines (osteopontin and angiopoietins 1 and 2) active in the bone marrow niche during the mobilisation of haematopoietic stem cells for autologous transplantation.Materials and methods
Forty-eight patients (24 females, 24 males), median age 56.5 years, entered the study. The group consisted of patients with multiple myeloma (n=34), lymphoma (n=13) and acute myeloid leukaemia (n=1). Blood samples were collected before chemotherapy and on the day of the first apheresis. Cytokines were evaluated by enzyme-linked immunosorbent assays. Additionally, circulating endothelial cells were assessed by flow cytometry.Results
The median concentration of angiopoietin 1 at the time of apheresis was lower than that at baseline (2.7 vs 7.8 ng/mL, p<0.001). In contrast, the median level of angiopoietin 2 increased during the mobilisation procedure (3.6 vs 2.8 ng/mL, p=0.001). The patients were divided according to the number of days of granulocyte colony-stimulating factor treatment before the first apheresis into “early” (<median=11 days) and “late” (>median) mobilisers. The group of “early mobilisers” had higher baseline angiopoietin 1 levels (median=11.6 ng/mL) than those of the “late mobilisers” (median=6.0 ng/mL, p=0.05). An adverse correlation was observed between duration of granulocyte colony-stimulating factor treatment and baseline angiopoietin 1 level. Baseline angiopoietin 1 levels correlated with numbers of circulating endothelial cells. Low angiopoietin 2 level increased the chance of poor mobilisation.Conclusions
The angiogenic processes can influence the timing of mobilisation. Angiopoietins 1 and 2 need further evaluation in the context of mobilisation. 相似文献16.
Background
Human bone marrow and umbilical cord blood are sources of allogeneic hematopoietic stem cells for transplantation, which is a life-saving treatment in a variety of diseases but is burdened by delayed T-cell reconstitution. Observational studies evaluating T-cell reconstitution in post-transplant recipients suggest that cord blood hematopoietic stem cells have a more effective capacity for T-cell reconstitution. This study focuses on the comparison of the capacity of cord blood and bone marrow hematopoietic stem cells to generate T cells in vitro.Design and Methods
Hematopoietic stem cells were cultured in OP9-delta-like-1 and OP9-green fluorescent protein co-cultures to estimate T and myeloid generation capacity, respectively. Phenotypic markers of T-lineage or myeloid differentiation were measured by flow cytometry and used to analyze their kinetics as a function of culture time. Hematopoietic stem cells were labeled with carboxyfluorescein diacetate succinamidyl ester and analyzed after culture to track their phenotypic progression in consecutive generations. Mixed OP9-delta-like-1 co-cultures were done with either carboxyfluorescein diacetate succinamidyl ester-labeled bone marrow and unlabeled cord blood hematopoietic stem cells, or vice versa, to evaluate their mutual influence on T-lineage differentiation. The T-cell potential of hematopoietic stem cells was addressed quantitatively by limiting dilution analysis.Results
Bulk cultures showed faster and more extensive T-cell differentiation by cord blood hematopoietic stem cells. Furthermore, the T-lymphoid differentiation capacity of cord blood and bone marrow hematopoietic stem cells can be discriminated very early based on the coordinated expression of CD34 and CD7. Mixing experiments with cord blood hematopoietic stem cells and bone marrow hematopoietic stem cells showed that these differences are cell intrinsic. Quantitative clonal analyses demonstrated that CD34+CD38−/lo hematopoietic stem cells from cord blood contained a two-fold higher T-lineage generation capacity than CD34+CD38−/lo bone marrow hematopoietic stem cells, whereas the myeloid differentiation was similar.Conclusions
Our data shows that cord blood hematopoietic stem cells have higher T-lymphoid differentiation potential than bone marrow hematopoietic stem cells and that this property is cell autonomous. 相似文献17.
Analysis of progenitor cell mobilization and erythropoietin plasma levels in patients with acute myocardial infarction
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Korff Krause Boris Fehse Kai Jaquet Claudia Lange Konstantin Kyriazis Sigrid Boczor Axel Zander Karl-Heinz Kuck 《Experimental & Clinical Cardiology》2005,10(2):104-107
BACKGROUND:
Experimental results from various animal models and preliminary clinical data have indicated the capacity of bone marrow-derived stem cells to home into infarcted heart tissue and promote cardiac repair. Erythropoietin (EPO) has been shown to increase the number of active endothelial progenitor cells in humans.OBJECTIVE:
To determine if mobilization of hematopoietic progenitor cells (CD34-positive [CD34+], CD117+ or CD133+ cells) into peripheral blood represents a physiological reaction during acute myocardial infarction (AMI) and if EPO is involved in the regulation of this process.METHODS:
Peripheral blood samples taken from 10 patients with AMI, seven patients with angina pectoris (AP) and five patients without coronary artery disease who underwent coronary angiography (controls) were analyzed for the presence of CD34+, CD117+ or CD133+ cells using flow cytometry. In addition, EPO plasma levels were determined by an ELISA. Samples were drawn between days 1 and 3 and days 4 and 8 after ischemic events.RESULTS:
Increased mean values of CD34+ and CD133+ cells were found in patients with either AMI or AP compared with the control group. Subjects with AMI had augmented cell counts of CD117+ and CD34+ progenitor cells compared with patients with AP. EPO levels were higher in patients with AMI or AP compared with the control group.CONCLUSIONS:
AMI in humans appears to serve as a stimulus for CD117+ and CD34+ progenitor cell mobilization. Increased EPO levels may play a role in the regulation of this process. 相似文献18.
Kikuta T Shimazaki C Ashihara E Sudo Y Hirai H Sumikuma T Yamagata N Inaba T Fujita N Kina T Nakagawa M 《Experimental hematology》2000,28(3):311-317
OBJECTIVE: One of the mechanisms for mobilization of hematopoietic stem cells and progenitor cells is alternation of adhesion molecules. We investigated the mobilization of hematopoietic progenitor cells in blood by administration of anti-vascular cell adhesion molecule (VCAM)-1 antibody (Ab) in mice. MATERIALS AND METHODS: Twelve- to 14-week old C57BL/6J mice were injected intravenously with anti-VCAM-1 Ab and anti-very late antigen (VLA)-4 Ab at a dose of 5 mg/kg for 2 days. RESULTS: The number of colony-forming cells (CFCs) in blood was increased 11.4-fold after anti-VCAM-1 Ab treatment, but the number of CFCs was not increased after treatment with anti-VLA-4 Ab. The number of colony-forming unit spleen (CFU-S) also was increased 21.6-fold in the peripheral blood by administration of anti-VCAM-1 Ab. The number of CFCs and CFU-S in the bone marrow of mice treated with anti-VCAM-1 Ab was decreased and that in the spleen also was decreased. On administration of recombinant human granulocyte colony-stimulating factor (125 microg/kg twice daily) with anti-VCAM-1 Ab, the numbers of CFCs and CFU-S were increased 141.8-fold and 439-fold, respectively. CONCLUSIONS: These observations demonstrated that administration of anti-VCAM-1 Ab induced mobilization of hematopoietic progenitor cells into blood from bone marrow and spleen and that granulocyte colony-stimulating factor has synergistic effects on anti-VCAM-1 Ab-induced mobilization. 相似文献
19.
José J Minguell Fernando M Florenzano Manuel R Ramírez Ramón F Martínez Gabriel P Lasala 《Experimental & Clinical Cardiology》2010,15(2):17-20
BACKGROUND:
Infusion of diverse types of bone marrow cells, as a source of endothelial progenitor cells (EPCs), into the ischemic myocardium is emerging as a promising therapy for coronary ischemia, probably mediated by the formation of new blood vessels. Studies have shown that while the procedure is safe and feasible, efficacy results are contentious. The investigators in the present preclinical translation study hypothesized that the infusion of a combination cell product consisting of EPCs and other cell types, such as mesenchymal stem cells, promotes the formation of more stable and mature blood vessels resulting in improved clinical outcomes. The safety and feasibility of the intracoronary infusion of such a cell combination was assessed in a canine model.METHODS:
A mixture of canine autologous mononuclear cells (as the source of EPCs) and ex vivo-expanded bone marrow-derived mesenchymal stem cells or a placebo solution were intracoronarily infused into healthy dogs. Follow-up after cell/placebo infusion included an electrocardiogram, serum cardiac enzyme testing, a transthoracic echocardiography and a histopathological heart examination.RESULTS:
On follow-up at all time points after infusion, no significant changes or abnormalities in vital signs, electrocardiogram, transthoracic echocardiography and heart histology were detected.CONCLUSIONS:
From a clinical perspective, the safety and feasibility of the protocol used in the present animal study demonstrated clinical relevance and provided direct evidence supporting the intracoronary infusion of combination stem/progenitor cell products. 相似文献20.
Beatriz Mart��n-Antonio Magdalena Carmona Jose Falantes Encarnaci��n Gil Alicia Baez Mar��a Suarez Pedro Mar��n Ildefonso Espigado ��lvaro Urbano-Ispizua 《Haematologica》2011,96(1):102-109