Cytokine-dependent long-term culture of highly enriched precursors of hematopoietic progenitor cells from human bone marrow.

Brandt, John E.; Srour, Edward F.; Besien, Koen van; Briddell, Robert A.; Hoffman, Ronald

doi:10.1172/jci114795

Cited by 158 publications

(59 citation statements)

References 49 publications

(22 reference statements)

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“…Previous studies on the role of stroma on hematopoiesis have primarily used long-term cultures [1][2][3][4][5][6][7][8]. This culture system promotes mainly myelopoiesis and lymphopoiesis while megakaryocytopoiesis is markedly suppressed due to the presence of transforming growth factor-β and β-thromboglobulin [20].…”

Section: Discussionmentioning

confidence: 99%

Stromal‐Conditioned Medium Synergizes with Thrombopoietin in Stimulating Megakaryocytopoiesis

Schattner

Cohen

1998

STEM CELLS

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We previously demonstrated that stromal cells release a soluble factor(s) that enhances thrombopoietin (TPO)-induced megakaryocyte (MK) production. We have now further characterized this enhancing activity of human bone marrow stroma and have also analyzed the role of direct contact of stromal cells with human bone marrow CD34 + cells on MK production. The three-to sixfold stromal-enhancing activity of conditioned media is constitutive and is not influenced by the presence of TPO. The addition of interleukins 3, 6 (IL-3, IL-6), stem cell factor (SCF), and TPO at concentrations found in stroma to a stroma-free system only enhanced by 58% the TPO-stimulated MK production. No influence of heparan sulfates on MK production was observed. In co-cultures of CD34 + cells in direct contact with stromal cells, nonadherent and adherent MK, and proplatelet structures were observed, either in the absence or presence of TPO. Direct contact did not further improve the enhancing activity of stromal cells on MK production induced by TPO. We conclude that the stromal enhancement of MK production is neither accounted for by stromal TPO, IL-3, IL-6, and SCF activities nor modified by physical contact. Stem Cells 1998;16:61-65 STEM CELLS 1998;16:61-65

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Section: Discussionmentioning

confidence: 99%

Stromal‐Conditioned Medium Synergizes with Thrombopoietin in Stimulating Megakaryocytopoiesis

Schattner

Cohen

1998

STEM CELLS

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“…12,13 Briefly, mononuclear cells from apheresis replication/differentiation of stromal and/or hematopoietic products and from BM harvests were density separated by precursors. 16,17 After removing non-adherent cells by centrifugation on Ficoll-Hypaque gradient (density = 1.077 replacing the medium (day 4 of culture), a small portion of g/cm 3 , Sigma Chemical, St Louis, MO, USA). Low-density attached nucleated cells was visualized in the culture plate.…”

Section: Ex Vivo Generation Of Stromal Cells From Mobilized Pbpc Harvmentioning

confidence: 99%

Detection of stromal cells in peripheral blood progenitor cell collections from breast cancer patients

Fernández

Simon

Herrera

et al. 1997

Bone Marrow Transplant

140

113

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Summary:been strengthened by several observations showing that growth factors (such as G-CSF, GM-CSF, IL-3 and SCF) modulate the expression or function of several cytoadhesive Transplantation of growth factor-mobilized peripheral blood progenitor cells (PBPC) is widely used in the molecules on the surface of hematopoietic progenitor cells. 8,9 In addition, cytokines produce profound morphotreatment of several neoplastic diseases. While in PBPC harvests the presence of several accessory immune and logical and immunohistochemical changes in marrow stroma and in the contiguous extracellular matrix. 10,11 tumor cells has been documented, that of stromal cells has not been reported. In the present study, we investiThese results suggest that marrow stroma should not be impervious to the effect of growth factors during PBPC gated for the presence of stromal cells in growth factormobilized PBPC harvests from breast cancer patients.mobilization procedures and raise the question of whether stromal cells are released from the marrow and conseLow-density cells from PBCP harvests in culture gave rise to an adherent layer containing fibroblast-like and quently are present in cytokine-mobilized PBPC harvests.In the present study, we monitored the presence of stromal large flat round cells. These cells express positive immunofluorescence staining for collagen I, collagen III, fibcells in growth factor-mobilized PBPC harvests from breast cancer patients. For this purpose, we used a two-step proronectin, VCAM-1 (CD106), ICAM-1 (CD54) and mesenchymal antigens recognized by monoclonal cedure which includes: (1)

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“…days 7-10 were established in 1 ml of complete medium in flat-bottomed 48-well plates, as previously described. 24,25 Reverse transcription and PCR analysis…”

Section: Short-term Cultures Of Total Cd34 + Cells Patientsmentioning

confidence: 99%

Preferential sequestration in vitro of BCR/ABL negative hematopoietic progenitor cells among cytokine nonresponsive CML marrow CD34+ cells

Veena

Cornetta

Davidson

et al. 1997

Bone Marrow Transplant

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Summary:cells. These studies also confirm the feasibility of employing negative hematopoietic regulators to augment the sequestration of normal HPC among the cytoIt is believed that long-term cultures of CML marrow cells favor the outgrowth of BCR/ABL negative hematokine nonresponsive fraction of CD34 ؉ cells, an approach that may be clinically feasible for autotranspoietic progenitor cells (HPC) primitive hematopoietic progenitor cells (HPC) within (MIP-1␣/CNR) supported a higher and, in some CML marrow. [7][8][9][10][11] The first documentation of the existence patients, a more extended production of clonogenic of normal primitive HPC in CML marrow was presented HPC, indicating that MIP-1␣ was able to maintain by Coulombel et al 12 who then went on to demonstrate that primitive HPC in a quiescent state. Predominance of although these cells remain dormant in vivo, they can be BCR/ABL negative progenitors in vitro was more eviactivated, and therefore detected and selected, in vitro. [13][14][15] al 10 and by our group 11 to be enriched for BCR/ABL their isolation from the more actively cycling leukemic negative HPC. Biological substances with inhibitory hematopoietic activities such as transforming growth factor-beta1 (TGF-

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Cytokine-dependent long-term culture of highly enriched precursors of hematopoietic progenitor cells from human bone marrow.

Cited by 158 publications

References 49 publications

Stromal‐Conditioned Medium Synergizes with Thrombopoietin in Stimulating Megakaryocytopoiesis

Stromal‐Conditioned Medium Synergizes with Thrombopoietin in Stimulating Megakaryocytopoiesis

Detection of stromal cells in peripheral blood progenitor cell collections from breast cancer patients

Preferential sequestration in vitro of BCR/ABL negative hematopoietic progenitor cells among cytokine nonresponsive CML marrow CD34+ cells

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