Self-renewal of factor-dependent hemopoietic progenitor cell-lines derived from long-term bone marrow cultures demonstrates significant mouse strain genotypic variation

1980 ◽  
Vol 13 (4) ◽  
pp. 501-511 ◽  
Author(s):  
Joel S. Greenberger
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Mouse Strain ◽  
Progenitor Cell ◽  
Genotypic Variation ◽  
Self Renewal ◽  
Bone Marrow Cultures ◽  
Hemopoietic Progenitor ◽  
Marrow Cultures

scholarly journals Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2269-2277 ◽  
Author(s):  
HM Lokhorst ◽  
T Lamme ◽  
M de Smet ◽  
S Klein ◽  
RA de Weger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Cell Lines ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Adherent Cells ◽  
Myeloma Cells ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

Abstract Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA- 5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.

scholarly journals Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2269-2277 ◽  
Author(s):  
HM Lokhorst ◽  
T Lamme ◽  
M de Smet ◽  
S Klein ◽  
RA de Weger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Cell Lines ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Adherent Cells ◽  
Myeloma Cells ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA- 5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.

Establishment of IL-5-Dependent Early B Cell Lines by Long-Term Bone Marrow Cultures

1989 ◽  
Vol 1 (2) ◽  
pp. 135-146 ◽  
Author(s):  
Akira Tominaga ◽  
Seiji Mita ◽  
Yuji Kikuchi ◽  
Yasumichi Hitoshi ◽  
Kiyoshi Takatsu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lines ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

Absence of nNOS Increases Longevity of Long Term Bone Marrow Cultures and Radiation Resistance.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4197-4197
Author(s):  
Shaonan Cao ◽  
Emily E. Greenberger ◽  
Michael W. Epperly ◽  
Anthony J. Kanai ◽  
Joel S. Greenberger
Keyword(s):  
Nitric Oxide ◽  
Cell Cycle ◽  
Bone Marrow ◽  
Cell Lines ◽  
Knockout Mice ◽  
Radiation Resistance ◽  
Irradiation Damage ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

Abstract Neuronal nitric oxide synthase (nNOS) has been shown to be localized to the mitochondrial membrane. The mitochondria play an important role in irradiation-induced apoptosis. Following irradiation, there is increased production of superoxide as well as an induction of nitric oxide in mitochondria. The combination of superoxide and nitric oxide results in production of peroxynitrite, a very strong oxidant that produces lipid peroxidation. Previous data have demonstrated that lack of nNOS protects the bladder from ionizing irradiation damage. To determine the role of nNOS in hematopoiesis, we established long term bone marrow cultures (LTBMCs) from nNOS deletion recombinant negative (knockout) mice as well as nNOS+/+ littermate mice. LTBMCs from nNOS knockout mice compared to +/+ control demonstrated increased total cumulative cell production (32.2 x 106 and 15.9 x 106 non-adherent cells, respectively), cobblestone island formation (5073 and 1106, respectively), and increased cumulative generation of day 14 CFU-GEMM colony forming cells per 105 plated (325 ± 30.4 and 9 ± 2.5 colonies, respectively) over 20 weeks in culture. IL-3 dependent non-adherent cell lines derived from the nNOS-/- and the nNOS+/+ cultures were tested for radiosensitivity. Cells from the nNOS−/− cell line demonstrated decreased radiation apoptosis 24 hours following irradiation, 5.89 ± 0.71% apoptotic cells compared to 10.42 ± 1.19% for the control littermates (p=0.041). Cell cycle analysis of littermate cells at 24 hours after 10 Gy demonstrated a G0/G1 and a G2/M block while there was no change in the cell cycle distribution of the nNOS−/− cells. The data demonstrate that absence of nNOS increases the longevity of hematopoiesis in LTBMCs and increases the radiation resistance of hematopoietic cell lines derived from such cultures.

Biology of Marrow Stromal Cell Lines Derived from Long-Term Bone Marrow Cultures of Trp53-Deficient Mice

1999 ◽  
Vol 152 (1) ◽  
pp. 29 ◽  
Author(s):  
Michael W. Epperly ◽  
Jenifer A. Bray ◽  
Timothy M. Carlos ◽  
Edward Prochownik ◽  
Joel S. Greenberger
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Stromal Cell ◽  
Marrow Stromal Cell ◽  
Bone Marrow Cultures ◽  
Deficient Mice ◽  
Marrow Cultures

scholarly journals Evolution of malignant plasmacytoma cell lines from K14E7 Fancd2−/− mouse long-term bone marrow cultures

Oncotarget ◽  
2016 ◽  
Vol 7 (42) ◽  
pp. 68449-68472
Author(s):  
Xichen Zhang ◽  
Wen Hou ◽  
Michael W. Epperly ◽  
Lora Rigatti ◽  
Hong Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Bone Marrow Cultures ◽  
Marrow Cultures
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