Improved hematopoiesis in anemic Sl/Sld mice by splenectomy and therapeutic transplantation of a hematopoietic microenvironment

Anklesaria, Pervin; FitzGerald, T.J.; Kase, Kenneth R.; Ohara, Akira; Js, Greenberger

doi:10.1182/blood.v74.3.1144.bloodjournal7431144

Cited by 11 publications

(16 citation statements)

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“…Several studies suggest that stromal cells in the bone marrow have immune‐modulatory effects that enhance HSC engraftment, induce donor‐specific tolerance and have a positive effect on autoimmune disorders in experimental animal models [29–32]. Human stromal cells also enhance long‐term haematopoietic engraftment after in utero transplantation in sheep [33].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Inhibit and Stimulate Mixed Lymphocyte Cultures and Mitogenic Responses Independently of the Major Histocompatibility Complex

Blanc¹,

et al. 2003

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We aimed to study the effects of mesenchymal stem cells (MSCs) on alloreactivity and effects of T-cell activation on human peripheral blood lymphocytes (PBLs) in vitro. MSCs were expanded from the bone marrow of healthy subjects. MSCs isolated from second to third passage were positive for CD166, CD105, CD44, CD29, SH-3 and SH-4, but negative for CD34 and CD45. MSCs cultured in osteogenic, adipogenic or chondrogenic media differentiated, respectively, into osteocytes, adipocytes or chondrocytes. MSC added to PBL cultures had various effects, ranging from slight inhibition to stimulation of DNA synthesis. The stimulation index (SI (PBL MSC)/ PBL) varied between 0.2 and 7.3. The SI was not affected by the MSC dose or by the addition of allogeneic or autologous MSCs to the lymphocytes.Suppression of proliferative activity was observed in all experiments after the addition of 10,000±40,000 MSCs to mixed lymphocyte cultures (MLCs). Lymphocyte proliferation was 10±90%, compared with a control MLC run in parallel without MSCs. In contrast, the addition of fewer MSCs (10±1000 cells) led to a less consistent suppression or a marked lymphocyte proliferation in several experiments, ranging from 40 to 190% of the maximal lymphocyte proliferation in control MLCs. The ability to inhibit or stimulate T-cell alloresponses appeared to be independent of the major histocompatibility complex, as results were similar using`third party' MSCs or MSCs that were autologous to the responder or stimulating PBLs. The strongest inhibitory effect was seen if MSCs were added at the beginning of the 6 day culture, and the effect declined if MSCs were added on day 3 or 5. Marked inhibitory effects of allogeneic and autologous MSCs (15,000) were also noted after mitogenic lymphocyte stimulation by phytohaemagglutinin (median lymphocyte proliferation of 30% of controls), Concanavalin A (56%) and protein A (65%). Little, if any, inhibition occurred after stimulation with pokeweed mitogen. Low numbers of MSCs (150 cells) were unable to inhibit mitogen-induced T-cell responses.MSCs have significant immune modulatory effects on MLCs and after mitogenic stimulation of PBL. High numbers of MSCs suppress alloreactive T cells, whereas very low numbers clearly stimulated lymphocyte proliferation in some experiments. The effect of a larger number of MSCs on MLCs seems more dependent on cell dose than histocompatibility and could result from an`overload' of a stimulatory mechanism.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Inhibit and Stimulate Mixed Lymphocyte Cultures and Mitogenic Responses Independently of the Major Histocompatibility Complex

Blanc¹,

et al. 2003

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“…Sl d encodes a biologically active secreted soluble SCF but lacks the membrane isoform due to an intragenic deletion of the transmembrane domain. Because the phenotype of Sl/Sl d mice revealed very severe deficiencies like reduced stem cell numbers and anemia (McCulloch et al, 1965;Anklesaria et al, 1989), the membrane form of SCF appears to be critical for normal function.…”

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confidence: 99%

Diverse isoforms of colony‐stimulating factor‐1 have different effects on the development of stroma‐dependent hematopoietic cells

Friel

Heberlein

Geldmacher

et al. 2005

Journal Cellular Physiology

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Maintenance and differentiation of hematopoietic stem and progenitor cells are controlled by complex interactions with the stroma microenvironment. Stroma-cell interactions can be supported by locally expressed membrane-spanning cell-surface (cs) growth factors. CSF-1 is expressed by stroma as a soluble glycoprotein, as proteoglycan, or as a membrane-spanning cs glycoprotein. CSF-1 regulates the survival, proliferation, and differentiation of mononuclear phagocytes. Whereas the biological role of soluble CSF-1 is well characterized, the function of the membrane-spanning cell-surface CSF-1 (csCSF-1) remains unclear. To analyze the biological significance of csCSF-1 in vitro, we used an epithelial cell line to ectopically express the different CSF-1 isoforms. In co-cultures of CSF-1 transduced epithelial cells with primary, early hematopoietic progenitor cells we examined whether interaction between csCSF-1 and its receptor mediates cell proliferation, self-renewal, or differentiation. csCSF-1 induces long-lasting proliferation of stimulated cells and furthermore supports self-renewal. Ectopic secretion of soluble CSF-1 does not permit long-term growth of progenitor cells but induces differentiation of monocytes into macrophages. Previously, we showed that the soluble and cs isoforms of stroma-encoded SCF differently affect the development of hematopoietic cells. Cell-surface SCF (csSCF) promotes self-renewal of stimulated cells whereas soluble SCF causes clonal extinction. These results and those presented here for CSF-1 provide evidence for diverse functions of the isoforms of the ligands SCF and CSF-1 for two tyrosine kinase receptors of the subclass III both regulating hematopoiesis on stroma.

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“…It may be assumed that in certain cases the transplanted marrow cells encounter a defective microenvironment. In murine models, Anklesaria et al had reported on improved hematopoiesis in irradiated mice and in anemic S 1/S Id mice as a result of transplantation and engraftment of a bone marrow stromal cell line (45,46). This fact emphasizes the importance of stromal elements in the correction of decreased or defective hematopoiesis.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow stromal elements in murine leukemia: Decreased CSF‐producing fibroblasts and normal IL‐1 expression by macrophages

Ben-Ishay¹,

Barak

Shoshan

et al. 1990

European J of Haematology

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A study of bone marrow stromal elements in murine acute myeloid leukemia (AML) was carried out. Our previous studies had indicated marrow stromal deficiency in murine AML. In the current investigation, separate stromal cells were cultured and the results obtained have shown that, while marrow stromal macrophages are normal in leukemia and express adequate amounts of IL‐1, the fibroblasts are markedly reduced. However, if sufficient fibroblasts are pooled in vitro, they produce adequate amounts of CSF. Test of TNFα in leukemic cells CM, as possible cause of marrow stromal inhibition in leukemia, had not disclosed this cytokine. Further, it was observed that total body lethal irradiation of leukemic mice aggravates the stromal deficiency, confirming results of our previous investigations. It is concluded that bone marrow stromal deficiency in murine AML is due to decreased fibroblasts and, implicitly, reduced CSF production.

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Improved hematopoiesis in anemic Sl/Sld mice by splenectomy and therapeutic transplantation of a hematopoietic microenvironment

Cited by 11 publications

References 0 publications

Mesenchymal Stem Cells Inhibit and Stimulate Mixed Lymphocyte Cultures and Mitogenic Responses Independently of the Major Histocompatibility Complex

Mesenchymal Stem Cells Inhibit and Stimulate Mixed Lymphocyte Cultures and Mitogenic Responses Independently of the Major Histocompatibility Complex

Diverse isoforms of colony‐stimulating factor‐1 have different effects on the development of stroma‐dependent hematopoietic cells

Bone marrow stromal elements in murine leukemia: Decreased CSF‐producing fibroblasts and normal IL‐1 expression by macrophages

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