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At least 937 records · Page 52Linked to original sources
PubMed1993

Cellular interactions in hemopoietic progenitor cell homing: a review.

Within the bone marrow microenvironment, dynamic cellular interactions are constantly occurring. These interactions involve hemopoietic stem cells, progenitor cells and maturing cells, physically interacting with other cells, some of which may function as accessory cells, and others which comprise the stromal elements; hemopoietic cells also interact with non-cellular elements, such as glycoproteins and fibrous proteins of the extracellular matrix (ECM). These interactions serve to regulate normal hemopoiesis by allowing the communication of regulatory information, migration and subsequent homing of stem cells within specific organs, and presentation of hemopoietic growth factors in a biologically relevant fashion. The goal of this review is to examine the specific cellular interactions that relate to the phenomenon of homing of intravenously transplanted stem cells to the bone marrow.

Amino Acid Sequence↗
PubMedDate not supplied

[Changes in the cellularity and lipid concentration of the bone marrow in rats after a single gamma-ray irradiation].

A study was made of the influence of gamma-irradiation of rats (14.4, 9.6, 7.2 and 4.8 Gy) on the number of nucleate cells, and the concentration of triacylglycerides (TG) and phospholipids (PL). Cellularity and concentration of PL decreased while that of TG increased under the effect of radiation. The degree of the changes in the above parameters was a function of dose and time after irradiation.

Animals↗
PubMed2003

[Development and repair of vessels from bone marrow stem cells in the adult: from biology to clinical practice].

In addition to its role in hematopoiesis, bone marrow appears to be a reservoir of stem cells that can differentiate into components of vessel wall. Upon stimulation by factors such as tissue ischemia, bone marrow stem cells can enter into circulating blood, and incorporate into areas of vascular development. Animal models suggest that bone marrow is a cellular source for tissue repair and/or regeneration. Data from humans, and clinical trials using bone marrow stem cells for the treatment of chronic ischemia in limbs and myocardium, support the view that stem cells may represent a new tool for the treatment of ischemia.

Adult↗
PubMed1997

Hematopoietic toxicity and cell cycle perturbations induced by new DNA minor groove-alkylating agents.

Some new alkylating agents which bind to the minor groove of DNA and have sequence-specific patterns of alkylation have shown anti-neoplastic activity in pre-clinical systems. Two of them, carzelesin and tallimustine, are now in phase II. Considering the severe dose-limiting bone marrow toxicity of both these drugs in clinical use, it was of interest to investigate the mechanism of their myelotoxicity in a detailed pre-clinical study and compare it with a conventional alkylating agent, such as melphalan. The origin and progression of the myelotoxicity of carzelesin, tallimustine and melphalan were investigated comparatively in mice, combining data on bone marrow and peripheral blood cellularity with data on the proliferative activity of bone marrow cells, obtained by in vivo administration of bromodeoxyuridine. Significant differences were found between the hematopoietic response to the 3 drugs, though all caused severe leukopenia. Carzelesin induced a short-term increase in myeloid proliferative activity, which prevented the high leukocytopenia on day 3 observed with the other drugs. However, when this effect was exhausted, a second nadir was seen in peripheral blood, with a new wave of cell proliferation of all lineages in the bone marrow. Reconstruction of the lymphoid lineage was slow for all 3 drugs but particularly difficult with high-dose tallimustine. In general, the hematopoietic system response to tallimustine was dampened, with no overshoots, suggesting either lasting effects or extensive cytotoxicity from the early to late precursors of all lineages.

Animals↗
PubMed2005

Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion.

Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.

Albumins↗
PubMed2003

Hematological cell findings in bone marrow and peripheral blood of rabbits after experimental acute exposure to Loxosceles intermedia (brown spider) venom.

The purpose of this work was to find out the cellular changes occurring in bone marrow and peripheral blood after acute exposure to the venom of Loxosceles intermedia. Doses of 40 microg of venom were injected intradermally into five rabbits, and five rabbits receiving only phosphate-buffered saline (PBS) were used as controls. Bone marrow and peripheral blood samples were obtained before the envenomation and 4, 8, 12, 24 and 48 h, and 5, 10, 15, 20 and 30 days after envenomation. In bone marrow samples we assessed cellularity, nucleated red cells, megakaryocytes and neutrophils, and in peripheral blood we assessed red cells (red cell concentration, hemoglobin and hematocrit), leukocytes, neutrophils and platelets. Our objective was to find out if the venom has a direct effect on bone marrow and peripheral blood or if changes in both of them are secondary to the needs of tissues, and if there is a good correlation between histopathological and hematological findings. We found that the red cell parameters were not affected by the venom, except for nucleated red cells which decreased after venom exposure. The depression of megakaryocyte numbers and thrombocytopenia showed a strong correlation with the histopathologic changes observed in skin biopsies obtained from the rabbits. The changes in cellularity and neutrophils of bone marrow were strongly correlated with those in peripheral blood and skin. The thrombocytopenia and neutropenia in peripheral blood are due to marrow depression, which may be a consequence of an extensive migration of platelets and neutrophils to the necrotic lesion or the marrow depression may be a transitory effect of evenoming by L. intermedia.

Animals↗
PubMed1998

Impairment of T and B cell development by treatment with a type I interferon.

Type I interferons alpha and beta, naturally produced regulators of cell growth and differentiation, have been shown to inhibit IL-7-induced growth and survival of B cell precursors in vitro. After confirming an inhibitory effect on B lymphopoiesis in an ex vivo assay, we treated newborn mice with an active IFN-alpha2/alpha1 hybrid molecule to assess its potential for regulating B and T cell development in vivo. Bone marrow and splenic cellularity was greatly reduced in the IFN-alpha2/alpha1-treated mice, and B lineage cells were reduced by >80%. The bone marrow progenitor population of CD43+B220+HSA- cells was unaffected, but development of the CD19+ pro-B cells and their B lineage progeny was severely impaired. Correspondingly, IL-7-responsive cells in the bone marrow were virtually eliminated by the interferon treatment. Thymus cellularity was also reduced by >80% in the treated mice. Phenotypic analysis of the residual thymocytes indicated that the inhibitory effect was exerted during the pro-T cell stage in differentiation. In IFN-alpha/beta receptor-/- mice, T and B cell development were unaffected by the IFN-alpha2/alpha1 treatment. The data suggest that type I interferons can reversibly inhibit early T and B cell development by opposing the essential IL-7 response.

Animals↗
PubMed1981

In vitro aging of human bone marrow derived stromal cells.

We have studied the in vitro cellular aging process in human bone marrow derived stromal cells. Two cell types, here called type I and type II, can be distinguished in the primary cell population. During subcultivation, resulting in aging in vitro, the type I cells gradually disappear, whereas the type II cells form an increasing fraction of the population. This observation is confirmed by cloning experiments, revealing that type I cells act as progenitor cells, giving rise to non-dividing type II cells. These results are best explained by the terminal differentiation theory as proposed by Martin et al.

Adult↗
PubMed1990

[Bone marrow biopsy in myeloproliferative syndromes: prognostic value of cellular quantification].

The proportion of granulocytes, erythroblasts, immature cells and megakaryocytes was evaluated when revising the bone-marrow biopsy specimens of 36 patients with myeloproliferative syndromes. These proportions were compared between themselves, a so-called Z value being thus attained; such value resulted from summing the proportion of granulocytes, megakaryocytes and immature cells and subtracting the proportion of erythroblasts. According to its value, above or below the mean, the Z figure correlates with the survival, the difference between both groups appearing as statistically significant (p = 0.02).

Biopsy↗
PubMed1983

Cadmium-induced immunotoxicity.

This study assessed the effects of cadmium on functional lymphopoietic precursor cells and cell size in both spleen and bone marrow. Splenic plaque-forming cell (S-PFC) precursors were stimulated by a thymus independent immunogen (TNP-LPS) and by a thymus dependent immunogen (TNP-BSA plus dextran sulfate). Bone marrow plaque-forming cell (M-PFC) precursors were stimulated by TNP-LPS plus dextran sulfate. Male C57Bl/6J mice received either a single ip injection of 5.9 mg/kg CdCl2, and were sacrificed 3 days later (ip group), or 5 daily sc injections of 3.26 mg/kg CdCl2, and were sacrificed either 2 days later (7 day sc group) or 7 days later (12 day sc group). The ip group showed an increase in spleen cellularity which resulted in an enhanced S-PFC (TNP-LPS) response per spleen and compensated for a depressed S-PFC (TNP-BSA) response per 10(6) cells cultured. Bone marrow cellularity was not significantly decreased but the M-PFC response was drastically depressed. Similar results were obtained in the 7 day sc group. However, a significant increase in spleen cellularity was not seen, resulting in a noncompensated decrease in S-PFC (TNP-BSA) response. The S-PFC (TNP-LPS) response per 10(6) cells cultured was increased in this group. Responses were similar to controls in the 12 day sc group, but bone marrow cellularity was decreased. The ip and 7 day sc groups showed substantial cadmium-induced shifts in bone marrow cell size distribution profile to larger diameters. Changes in spleen cell size distribution were not as significant. Partial recovery was evident in the 12 day sc group. This study demonstrated that in vivo exposure to cadmium has a greater effect on the in vitro function of immature B-cells in the bone marrow than on more mature B-cells found in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Growth hormone exerts hematopoietic growth-promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine.

Recombinant human growth hormone (rhGH) was administered to mice to determine its effect on hematopoiesis. BALB/c mice and mice with severe combined immune deficiency (SCID), which lack T cells and B cells, were administered intraperitoneal injections of rhGH for 7 days. Upon analysis, both strains of mice exhibited an increase in splenic and bone marrow hematopoietic progenitor cell content and cellularity, indicating that rhGH can act as a hematopoietic growth factor. C57BL/6 mice were then placed on azidothymidine (AZT). AZT is a reverse transcriptase inhibitor currently used as a treatment for acquired immune deficiency syndrome (AIDS), but which also produces significant myelotoxic effects. Treatment of mice with rhGH partially counteracted the myelosuppressive properties of AZT. Bone marrow cellularity, hematocrit values, white blood cell counts, and splenic hematopoietic progenitor cell content were all significantly increased if rhGH (20 micrograms injected intraperitoneally every other day) was concurrently administered with AZT. Administration of ovine GH (ovGH), which, unlike rhGH, has no effect on murine prolactin receptors, also prevented the erythroid-suppressive effects of AZT in mice, but had no significant effect on granulocyte counts. Thus, the effects of GH are mediated at least in part through GH receptors in vivo. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of ovGH resulted in an increase in splenic hematopoietic progenitor cells. No significant pathologic effects were observed in mice receiving either repeated rhGH or ovGH injections. Thus, GH exerts significant direct hematopoietic growth-promoting effects in vivo and may be of potential clinical use to promote hematopoiesis in the face of myelotoxic therapy.

Animals↗
PubMed1987

Leishmania mexicana: a cytochemical and quantitative study of lysosomal enzymes in infected rat bone marrow-derived macrophages.

The cellular localization and activity of the lysosomal enzymes acid phosphatase, trimetaphosphatase, and arylsulfatase were studied in rat bone marrow-derived macrophages infected with Leishmania mexicana amazonensis amastigotes. The specific activity of acid phosphatase normalized for protein content was similar in normal macrophages and in isolated amastigotes, whereas the latter were markedly deficient in trimetaphosphatase and arylsulfatase activities. It is thus likely that trimetaphosphatase and arylsulfatase activities detected in infected macrophages were of host cell origin. The activities of the three enzymes, assayed biochemically, varied independently in the infected macrophages. While arylsulfatase activity was unchanged after infection, the activity of acid phosphatase increased by 19, 40, and 94% at 6, 24, and 48 hr, respectively. Trimetaphosphatase activity rose only slightly during the first 24 hr after infection but increased by 74% at 48 hr. The rise in acid phosphatase activity could be accounted for only partially by multiplication of the amastigotes. Thus, as for trimetaphosphatase, these results suggest enhanced macrophage synthesis of acid phosphatase and/or reduced enzyme degradation by the infected macrophages. The reduction in host cell lysosomes previously described (Ryter et al. 1983; Barbieri et al. 1985) was confirmed but appearance of lysosomal enzyme activity in the parasitophorous vacuole is documented in the present report. Thus, Leishmania do not seem to reduce the amount and the activity of host lysosomal enzymes.

Acid Anhydride Hydrolases↗
PubMedDate not supplied

[Evolution of acute leukemia in myelodysplastic syndromes: prognostic histopathological factors in a series of bone marrow biopsies].

Out of 9,324 bone marrow biopsies, 250 cases of myelodysplastic syndromes (MDS) and 514 of acute non-lymphoid leukemia (AL) were collected. Twenty AL represented an evolution of MDS: the marrow had a mean cellularity of 58.5%, a mean percentage of blasts of 19% (55% of the cases had more than 10% of blasts in the marrow); only in one case (5%) benign lymphoid nodules (LN) were present. In 42 cases of MDS deceased without an evolution to overt AL, the bone marrow showed a cellularity of 60%, a mean percentage of blasts of 14% (only 29% had more than 10% of blasts); in 13 cases (31%) LN were present. Our data indicate that the percentage of bone marrow blasts is the most significant criterion for predicting an evolution to AL, although in the single case such evolution is not foreseeable. The presence of LN mostly in MDS without a leukemic progression could indicate a protective effect of NL, perhaps by means of an immunologic mechanism.

Acute Disease↗
PubMed1990

Observations on the haemopoietic response to critical illness.

Peripheral blood cytopenias are common in patients receiving intensive care, particularly in those with multiple organ failure. To assess the contribution of bone marrow hypoplasia in such patients 44 bone marrow samples from 24 patients under intensive care were studied by standard morphological techniques and by the granulocyte-macrophage colony forming cell (GM-CFC) assay. Frequently observed morphological abnormalities in the bone marrow included the following: (i) a reduction in overall cellularity in seven patients, with a progressive decrease in most patients studied sequentially; (ii) an increase in the number of actively phagocytic macrophages; and (iii) a disruption of normal bone marrow architecture with the accumulation of intercellular hyaluronic acid glycosaminoglycan. Mean GM-CFC growth was significantly reduced when compared with that in a group of normal controls. In four of five patients studied sequentially GM-CFC growth became subnormal in association with a reduction in bone marrow cellularity. Inhibitory serum factors were not identified. These morphological abnormalities are similar to the changes observed in gelatinous degeneration of the bone marrow. In both situations disruption of the haemopoietic microenvironment, with the accumulation of hyaluronic acid proteoglycan, may be an important factor in the inhibition of haemopoietic progenitor cell growth. The proliferation of macrophages, by the release of a variety of cytokines or reactive oxygen intermediates, may also be implicated in impaired haemopoiesis and the development of disordered erythropoiesis.

Adolescent↗
PubMed2000

Human bone marrow stromal cell: coexpression of markers specific for multiple mesenchymal cell lineages.

The role of hematopoietic stem cells in blood cell development is reasonably understood, whereas the identity and the function of bone marrow stromal cells are much less clear. Using stromal cells in bone marrow cultures of the Dexter type, a favorite medium for the study of hematopoiesis, we show that stromal cells actually represent a unique cell type. Conventional wisdom has held that stromal cells in Dexter cultures comprise a mixture of macrophages, hematopoietic cells, adipocytes, osteoblasts, fibroblasts, muscle cells, and endothelial cells. Our findings demonstrate that Dexter cultures consist of three cell types: macrophages ( approximately 35%), hematopoietic cells ( approximately 5%), and nonhematopoietic cells ( approximately 60%). We have purified the nonhematopoietic cells free of macrophages and hematopoietic cells to produce compelling evidence that they in fact represent a single cell type (multidifferentiated mesenchymal progenitor cell, MPC) which coexpresses genes specific for various mesenchymal cell lineages including adipocytes, osteoblasts, fibroblasts, and muscle cells. We further show that these multi- or pluridifferentiated MPCs are capable of supporting hematopoiesis by demonstrating the expression of several hematopoietic growth factors and extracellular matrix receptors including G-CSF, SCF, VCAM-1, ICAM-1, and ALCAM. Since the MPCs can be easily purified to near homogeneity (95%), they can be of value in enhancing engraftment of hematopoietic stem cells. Also, this new understanding of bone marrow stromal cells as "one cell with many different faces" promises to advance our knowledge of regulatory cellular interactions within bone marrow.

Bone Marrow Cells↗