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1.
Homing receptor is a membrane lectin of 110 kd molecular weight that recognizes galactosyl and mannosyl residues of an as yet unknown glycoconjugate. It is responsible for recognition and selective homing of hemopoietic progenitor cells after these cells are transplanted intravenously. Consequently, it is present on the surface of hemopoietic progenitor cells. To determine the distribution of this receptor on other cell types we performed standard binding assays in many cell types using galactosyl and mannosyl residues covalently bound to bovine serum albumin (G-BSA and M-BSA) as an index of homing receptor. BSA moiety was then labeled with 125I. The three cloned hemopoietic cell lines B6Sut, FDCP-1, and FDCP-mix all showed combined binding of G-BSA and M-BSA, whereas the lymphoid cell line L1210 showed only M-BSA, not G-BSA binding and, therefore, was considered to lack homing receptors. Similarly, stromal cell lines D2X and GB1/6 as well as primary marrow stroma (progenitor cell-depleted) did not show homing receptors as evidenced by combined binding of G-BSA and M-BSA. Nor did the nonhemopoietic stromal cell line Swiss 3T3 show the presence of homing receptors by these criteria. We conclude that homing receptors are distributed narrowly and are present on hemopoietic progenitor cells, but absent on hemopoietic stroma. 相似文献
2.
Antisera were raised by immunizing rabbits with cloned lines of murine hemopoietic progenitor cells (P cells) that depended on the presence of a specific hemopoietic growth factor, persisting cell-stimulating factor (PSF), for their growth and survival. The unabsorbed antiserum was inhibitory, but after absorption with murine spleen cells and the mastocytoma, P815, significant stimulation of both P cell growth and thymidine incorporation was evident. IgG antibodies isolated from the antiserum by staphylococcal protein A chromatography or further purified by diethylaminoethyl anion exchange chromatography, ammonium sulphate precipitation, and gel filtration using Sephacryl S-300 were responsible for the stimulation. The absorbed antiserum promoted the survival of normal murine bone marrow cells in liquid culture over a four-day period, and the inclusion of IgG antibodies in agar cultures of normal bone marrow promoted the in vitro survival, over a 48-hour period, of cells capable of subsequently generating, in the presence of a source of PSF, colonies of neutrophils, macrophages, and megakaryocytes. It is postulated that the antibodies act by stimulating the PSF receptor on both the factor-dependent cell lines and normal myeloid progenitor cells. 相似文献
3.
Origin of hemopoietic stem cells in embryonic bursa of Fabricius and bone marrow studied through interspecific chimeras. 总被引:7,自引:2,他引:7 下载免费PDF全文
N M Le Douarin E Houssaint F V Jotereau M Belo 《Proceedings of the National Academy of Sciences of the United States of America》1975,72(7):2701-2705
The histogenesis of the bursa of Fabricius and of bone marrow was studied by a biological cell marking technique based on differences in the nuclear structure of two species of birds, Japanese quail (Coturnix coturnix japonica) and chick (Gallus gallus). In quail cells the nucleus contains a large amount of heterochromatin associated with the nucleolus. That makes it possible to distinguish them from chick cells after Feulgen-Rossenbeck staining and by electron microscopy. By grafting bursal rudiments and limb buds of quail into chick and inversely it was possible to demonstrate that the whole hemopoietic population of the bursa of Fabricius and of bone marrow is derived from bloodborne extrinsic stem cells. Neither endoderm nor mesoderm of the bursal rudiments is capable of differentiating into lymphoid cells. Combinations of quail bursal endoderm with chick homologous mesenchyme showed that the reticular cells of the follicles are the only endodermal derivatives of the bursa. The mesenchymal bursal component gives rise to the interfollicular connective cells. The contribution to bone marrow histogenesis of cells of vascular and blood origin, on one hand, and of the elements of the cartilaginous model, on the other hand, was analyzed. It appeared that osteoblasts, osteocytes, and stromal cells of marrow are derived from the perichondrium. In contrast, the endothelium of the vascular buds and the hemopoietic cells which invade the diaphysal cartilage during the endochondral ossification process do not belong to the mesenchymal bone primordium but have a fully extrinsic origin. 相似文献
4.
G Bogliolo R Lerza M Mencoboni A Saviane I Pannacciulli 《Experimental hematology》1988,16(11):938-940
The toxicity of the antiviral drug 3'-azido-3'-deoxythymidine was studied in vivo on murine hemopoietic progenitor cells and peripheral blood cells. The drug induced a marked decrease of all tested populations, showing a severe toxicity on hemopoiesis. 相似文献
5.
K. Geissler W. Hinterberger U. Jäger P. Bettelheim E. Neumann O. Haas P. Ambros A. Chott T. Radaszkiewicz K. Lechner 《Annals of hematology》1988,57(1):45-49
Summary Pluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n=3; RA with ring sideroblasts (RARS), n=3; RA with excess of blasts (RAEB), n=8; RA with excess of blasts in transformation (RAEBt), n=7; chronic myelomonocytic leukemia (CMML), n=2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients. 相似文献
6.
7.
Multipotent adult progenitor cells (MAPCs) are bone marrow-derived stem cells that have extensive in vitro expansion capacity and can differentiate in vivo and in vitro into tissue cells of all 3 germinal layers: ectoderm, mesoderm, and endoderm. The origin of MAPCs within bone marrow is unknown. MAPCs are believed to be derived from the bone marrow stroma compartment as they are isolated within the adherent cell component. Numerous studies of bone marrow chimeras in the human and the mouse point to a host origin of bone marrow stromal cells. Mesenchymal stem cells (MSCs), which coexist with stromal cells, have also been proven to be of host origin after allogeneic bone marrow transplantation in numerous studies. We report here that following syngeneic bone marrow transplants into lethally irradiated C57BL6 mice, MAPCs are of donor origin. 相似文献
8.
High levels of committed erythroid and granulocytic/monocytic progenitor cells have been demonstrated in fresh blood obtained at fetoscopy. The fetal progenitor cells were more sensitive to appropriate stimuli (erythropoietin and colony-stimulating factor) than adult progenitor cells grown under the same conditions, and this was shown to be due to intrinsic differences in the progenitor cells at the different developmental stages. 相似文献
9.
The origin of spleen colony-forming units (CFUs) and fibroblastoid colony-forming cells (CFUF) repopulating the marrow of femurs subcutaneously implanted in syngeneic and semi-syngeneic mice was studied by making use of a chromosome marker for CFUs and a cytotoxicity test for CFUF. The CFUs present in implants during first 4 weeks were of a mixture of those from the donor and the host, and thereafter, were exclusively of host origin. On the other hand, the colony growth of CFUF from the marrow of C57BL/6 femurs grafted in B6CBAF1 mice remained almost totally unaffected by treatment with C57BL/6 anti-B6CBAF1 serum as late as 40 weeks after implantation. Quite similar results were obtained from the marrow-depleted femur implants. It is concluded from the present studies that chimeric marrow consisting of hemopoietic cells of host origin and stromal cells of donor origin can repopulate the femurs within a matter of several weeks after subcutaneous implantation. 相似文献
10.
T Otsuka S Okamura M Harada N Ohhara S Hayashi S Yamaga K Nagasawa Y Niho 《The Journal of rheumatology》1988,15(7):1085-1090
Hematologic abnormalities in patients with systemic lupus erythematosus (SLE) were studied before treatment, using an in vitro bone marrow progenitor cell assay. In 10 patients with SLE, there was a decrease in the number of multipotent hemopoietic colonies. Multipotent colony formation was suppressed by the addition of T cells from the patients with SLE. The culture supernatant of phytohemagglutinin stimulated SLE leukocytes had diminished activity to support the multipotent colony formation. These results suggest that the hematologic abnormalities in SLE occur at the multipotent stem cell level. The T cell mediated suppression of hemopoietic progenitor cells and the diminished activity of humoral factors released from SLE leukocytes may play some role in the pathogenesis of hematologic abnormalities in SLE. 相似文献
11.
12.
M P Bodger 《Experimental hematology》1987,15(8):869-876
A two-stage procedure to enrich hemopoietic progenitor cells from human umbilical cord blood is described. Mononuclear cells isolated from 60% Percoll gradients were first treated with a panel of monoclonal antibodies and complement to remove lymphoid and myeloid cells and granulocyte-macrophage colony-forming cells (CFU-GM) and their immature progeny. Cells stained with monoclonal antibody RFB-1 were separated on the fluorescence-activated cell sorter and cultured in the mixed-colony assay. Progenitor cells were isolated in a high RFB-1 antigen density cell fraction containing greater than 95% undifferentiated blast cells and 32% +/- 12% colony-forming cells. Pluripotential progenitor cells (CFU mix) were enriched 229-fold and accounted for 3.2% +/- 1.2% of the isolated cells. Erythroid progenitor cells (BFU-E) were enriched 204-fold and accounted for 20.8% +/- 8.4% of the isolated cells. The procedure recovered 114% +/- 32% of CFU mix but the number of CFU mix in unseparated cord blood appears to be underestimated due to the presence of granulocytic cells identified by monoclonal antibody CMRF-7 (CD15) that decrease the cloning efficiency of CFU mix. Removal of CD15+ cells yielded a four- to fivefold improvement in the plating efficiency of CFU mix. Mixed-colony formation was completed in 9-11 days in cultures inoculated with enriched progenitor cell fractions, compared with 14-16 days in cultures of unseparated cord blood. The enriched progenitor cells could be useful for studying the regulation of hemopoiesis by recombinant growth factors. 相似文献
13.
Pluripotent hemopoietic progenitor cells (CFU-GEMM, cells forming mixed hemopoietic colonies in methylcellulose) from human bone marrow were enriched 90-fold by positive selection on the fluorescence-activated cell sorter using monoclonal antibody RFB-1. Bone marrow cells were separated by cell size, using log 90 degrees light scatter, and the cell fraction containing CFU-GEMM was further separated by relative fluorescence intensity for the RFB-1 antigen. Further enrichment, up to 150-fold, was achieved by depleting bone marrow of T cells and mature myeloid cells prior to RFB-1 selection. These procedures yield a cell fraction containing 51% blast cells, 2% promyelocytes, and 47% undifferentiated (lymphocyte-like) mononuclear cells, although only 1% of the cells formed a mixed colony. CFU-GEMM are strongly positive for the RFB-1 antigen, whereas morphologically identifiable erythroblasts, myeloblasts, and promyelocytes are weakly RFB-1+. This suggests that the relative concentration of the RFB-1 antigen on bone marrow cells is inversely related to their maturity. The greatly increased recovery of CFU-GEMM after the separation of bone marrow by log 90 degrees light scatter and the removal of T cells and mature myeloid cells suggested that accessory cells that normally regulate the cloning efficiency of CFU-GEMM were removed. 相似文献
14.
Colony formation by primitive hemopoietic progenitor cells in serum-free medium. 总被引:3,自引:1,他引:3 下载免费PDF全文
J F Eliason N Odartchenko 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(3):775-779
A serum-free medium has been developed for clonal growth of murine hemopoietic progenitor cells. In this medium, the number of nonerythroid colonies induced by factors produced by cloned T lymphocytes was 90 +/- 10% of the number generated in serum-containing medium. Erythroid colony number in serum-free cultures containing the T-cell factors but no exogenous erythropoietin was significantly higher than that in cultures with serum, and the cloning efficiency was independent of cell concentration. Further addition of erythropoietin increased erythroid colony number approximately equal to 4-fold. Pure erythropoietin alone stimulated erythroid colony formation, but the cloning efficiency was highly dependent on cell concentration. Analysis of individual colonies generated in serum-free cultures containing the T-cell factors indicated that some contained cells of several hemopoietic lineages, demonstrating that multipotential progenitors can give rise to colonies in this system. 相似文献
15.
We used a complement-dependent cytotoxic assay to study the expression of DR antigens by hemopoietic progenitor cells derived from normal marrow and from the blood of patients with chronic phase chronic myeloid leukemia (CML). Almost all normal and CML day-12 granulocyte-macrophage colony-forming cells (d12 GM-CFC) and erythroid burst-forming units (BFU-E) expressed DR antigens. A primitive progenitor cell, the "blast colony-forming cell" (Bl-CFC), also expressed DR antigens whether derived from normal marrow or CML blood. The expression of DR antigen by normal and CML Bl-CFC was similar but the density of DR antigens on CML d12 GM-CFC and BFU-E was much greater than that of their counterparts from normal marrow. The similarity in DR antigen density on normal and CML Bl-CFC means that purging of CML marrow using a DR-specific antibody would not select in favor of normal cells and thus would not be useful in an autograft setting. 相似文献
16.
A Porcellini A Manna N Talevi G Sparaventi M T Marchetti-Rossi D Baronciani M De Biagi 《Experimental hematology》1984,12(11):863-866
The studies described herein were undertaken to help define the effects of certain cyclophosphamide derivatives that have been used for selective removal of leukemic cells from marrow samples used for autologous transplantation. We have tested the effect of 4-HC and another cyclophosphamide congener, ASTA-Z 7557, on pluripotent stem cells (CFU-S) and committed progenitor cells (CFU-GM) in mice. The CFU-S were evaluated by the spleen colony assay at eight days and 12 days after transplant. The eight-day colonies are transient in nature, rapidly growing, mainly erythroid, and lack pluripotential precursors. The 12-day colonies are believed to provide a measure of hemopoietic stem cells as they slowly grow and do contain primitive precursors. Our data show that at the maximum dose levels tested, both drugs caused a 100% loss of CFU-GM and about 80%-95% inhibition of early transient CFU-S. In contrast, about 70% of the pluripotent 12-day CFU-S were spared. These data appear to explain the hemopoietic recovery seen in man after transplantation with marrow cells treated with 4-HC despite their relative absence of hemopoietic progenitor cells. 相似文献
17.
The effect of the antitumorally active hexadecylphosphocholine (He-PC) on the colony-stimulating factor (CSF)-dependent growth of human hemopoietic progenitor cells was studied. At low concentrations He-PC stimulated the CSF-dependent progenitor cell colony growth of three patients suffering from chronic myeloid leukemia (CML) and of three of six patients without hematological disorders. The stimulating effect was up to eight times that of the control using granulocyte colony-stimulating factor (G-CSF) and twofold in the case of granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas only slight effects were noted when interleukin 3 (IL-3) or the combination of the CSFs was used as an additive. The stimulatory effects observed are far below the He-PC concentrations that are usually required for the in vitro growth arrest of cancer cells. At higher concentrations He-PC displayed suppressive effects, most pronounced in the case of G-CSF-dependent colony growth. At the concentrations investigated, He-PC failed to show any changes in the composition and distribution of specific colonies. He-PC by itself had no mitogenic activity. This indicates that He-PC acts as a co-stimulator. In the cases of myeloproliferative diseases and in the case of a patient without known hematological disorder, removal of accessory cells did not abrogate the He-PC-enhanced colony growth by CSFs. Thus, the stimulatory effect of low-dose He-PC seems not to be mediated by accessory cells. 相似文献
18.
Surface phenotypes of human hemopoietic progenitor cells defined by monoclonal antibodies 总被引:3,自引:0,他引:3
A panel of ten monoclonal antibodies which react with antigens present on the surface of myeloid leukemic cells was used to investigate the distribution of these antigens on normal hemopoietic stem cells and progenitor cells at various stages of maturity. A population of immature cells, possibly stem cells, that are capable of regenerating CFU-GM in long-term marrow cultures reacts with four antibodies recognizing antigens abundantly expressed in leukemic cells, but does not react with antibodies against Ia-like molecules or against carbohydrate determinants specific for myeloid cells. Progenitor cells that form mixed colonies in semisolid medium (CFU-GEMM), early erythroid (BFU-E) and early myelomonocytic (type 1 CFU-GM) progenitors retain the antigens present on the hypothetical stem cell population and begin to express Ia-like antigens. As they differentiate, myeloid and erythroid progenitors undergo a series of quantitative and qualitative shifts in surface phenotype. They begin to express stage- related, lineage-specific antigens and cease expressing antigens common to early cells of different lineages. The identification of antigens present on very immature normal progenitor cells should be valuable in future studies aimed at the detailed characterization of this relatively little-known hemopoietic cell population. 相似文献
19.
Selective accumulation of lymphocyte precursor cells mediated by stromal cells of hemopoietic origin
M Tamir R Eren A Globerson E Kedar E Epstein N Trainin D Zipori 《Experimental hematology》1990,18(4):322-340
Thymocytes were propagated in long-term cultures supported by stromal cells of both bone marrow and thymus origin. Interleukin 2 (IL-2) supplementation augmented the cell yield and allowed detailed phenotype analysis. Within 2-3 months of culture a cell population was selected in which the expression of Thy-1 antigen persisted, CD4 and CD8 antigens gradually declined, and Pgp-1 antigen, found on less than 5% of fresh thymocytes, was strongly increased. This cultured cell population (Thy-1.2 origin) contained no detectable spleen colony-forming units (CFU-S) but efficiently repopulated the thymus of Thy-1.1-irradiated congenic mice, indicating the precursor T-cell nature of the population. Upon removal from the stroma, the T cells exhibited poor cytotoxicity towards syngeneic tumor cells. Further propagation with IL-2 in the absence of stroma resulted in the acquisition of cytotoxic ability. Replacement of the horse serum used in the above experiments with fetal calf serum resulted in accumulation of cells expressing B220 antigen. This experimental model provides the means to maintain lymphocyte precursor cells in long-term culture and to further study their differentiation in the absence of stroma, both in vitro and in vivo. 相似文献
20.
Selective resistance of bone marrow-derived hemopoietic progenitor cells to gliotoxin. 总被引:3,自引:0,他引:3 下载免费PDF全文
A Müllbacher D Hume A W Braithwaite P Waring R D Eichner 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(11):3822-3825
The fungal metabolite gliotoxin at low concentrations prevents mitogen stimulation of mature lymphocytes as a result of gliotoxin-induced genomic DNA degradation. Bone marrow, on the other hand, contains a subpopulation of cells resistant to gliotoxin at similar concentrations. This population includes the hemopoietic progenitor cells that grow in vitro in response to appropriate colony-stimulating factors and cells that form colonies in the spleens of lethally irradiated recipients. Gliotoxin treatment of lymph node cell-enriched bone marrow significantly delayed the onset of graft-versus-host disease in fully allogeneic bone marrow chimeras. 相似文献