scholarly journals IN VITRO STUDIES ON RADIATION LYMPHOID RECOVERY OF MOUSE SPLEEN

1966 ◽  
Vol 123 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Amiela Globerson
Keyword(s):  
Bone Marrow ◽  
Organ Culture ◽  
Culture Method ◽  
Lymphoid Cells ◽  
In Vitro Studies ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Stimulation Of

In vitro studies, utilizing an organ culture method were reported on mutual interactions between irradiated spleen, normal bone marrow, and thymus. It has been shown; (a) that singly isolated spleen explants were incapable of lymphoid regeneration, (b) thymus had no stimulatory effect on spleen regeneration, (c) bone marrow interacted synergistically with spleen leading to appearance of lymphoid cells which were not detected in singly isolated bone marrow or spleen, and (d) no stimulation of lymphopoiesis in bone marrow was conferred by thymus in the absence of spleen. The results are discussed in terms of possible mechanisms involved in lymphoid radiation recovery in vivo.

in vitro studies with melphalan and pediatric neoplastic and normal bone marrow cells

1986 ◽  
Vol 37 (6) ◽  
pp. 819-823 ◽  
Author(s):  
Diana A. Worthington-White ◽  
John R. Graham-Pole ◽  
Susan A. Stout ◽  
Christopher M. Riley
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
In Vitro Studies ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Marrow Cells

Radiation Modifying Effect of the Free Radical Norpseudopelletierene-N-Oxyl on Normal Bone Marrow Stem Cells in Vitro and in Vivo

1974 ◽  
Vol 58 (3) ◽  
pp. 361 ◽  
Author(s):  
N. M. Blackett ◽  
W. E. Wooliscroft ◽  
E. M. Fielden ◽  
S. C. Lillicrap
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Free Radical ◽  
Bone Marrow Stem Cells ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Modifying Effect

STIMULATION OF BONE MARROW CELLS AND BONE FORMATION BY NACRE. IN VIVO AND IN VITRO STUDIES

Bioceramics ◽  
1999 ◽  
Author(s):  
M. Lamghari ◽  
S. Berland ◽  
A. Laurent ◽  
H. Huet ◽  
M.J. Almeida ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Marrow Cells ◽  
In Vitro Studies ◽  
Stimulation Of ◽  
Marrow Cells

scholarly journals HEMOPOIETIC SPLEEN COLONY STUDIES

1967 ◽  
Vol 126 (5) ◽  
pp. 819-832 ◽  
Author(s):  
J. L. Curry ◽  
J. J. Trentin
Keyword(s):  
Bone Marrow ◽  
Cell Types ◽  
Slight Reduction ◽  
Normal Bone Marrow ◽  
Mixed Cell ◽  
Colony Forming Unit ◽  
Normal Bone ◽  
Endogenous Spleen Colonies

The effects of phytohemagglutinin (PHA) were studied in irradiated mice to see if a definite myeloproliferative effect could be demonstrated in vivo. The data obtained suggested the following conclusions. PHA treatment of the bone marrow donor only, causes a consistent but slight reduction in transplantable spleen colony-forming unit (CFU) content of the bone marrow 24 hr after the last PHA injection, but no change was found in the proportion of the various colony types. PHA treatment of the irradiated recipient of normal bone marrow causes no change in the number of spleen colonies. However, 8-day colonies are only about half normal size, are much more likely to be of mixed cell types, contain many large undifferentiated blastoid cells, but fewer transplantable CFU. The spleen sinusoids are packed with hemopoietic cells. Spleen colonies developing in hosts receiving daily injections of PHA show, in addition to the usual spectrum of cell types, a high proportion of unusual blastoid cells resembling the PHA transformed peripheral lymphocytes seen in vitro. The function of these cells is not known, but they may represent augmented proliferation and/or transformation of stem cells. PHA administered after irradiation significantly increased the number of endogenous spleen colonies, and, at certain doses of irradiation, improved postirradiation survival. PHA administered before irradiation had no effect on the number of endogenous spleen colonies formed, or on postirradiation survival. On the basis of these and other data, possible modes of action of PHA are discussed.

Stimulation of bone marrow cells and bone formation by nacre: in vivo and in vitro studies

Bone ◽  
1999 ◽  
Vol 25 (2) ◽  
pp. 91S-94S ◽  
Author(s):  
M Lamghari ◽  
M.J Almeida ◽  
S Berland ◽  
H Huet ◽  
A Laurent ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Marrow Cells ◽  
In Vitro Studies ◽  
Stimulation Of ◽  
Marrow Cells

scholarly journals A Novel in Vitro Three Organ System Assay Identifies a Small Molecule Ubiquitin Analog with in Vivo Activity Against Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2085-2085
Author(s):  
Sergei Vatolin ◽  
James G Phillips ◽  
Shravya Govindgari ◽  
Dale Grabowski ◽  
Yvonne Parker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Small Molecule ◽  
Organ System ◽  
Normal Bone Marrow ◽  
Myeloma Cells ◽  
Normal Bone ◽  
Protein Ubiquitination

Abstract Taking a mechanistically unbiased approach to the discovery of new myeloma drugs we developed a three organ system assay that selected anti-myeloma compounds from a primary 30,000 small molecule ATP-based screen in one “sandwich” setup for tolerability by normal bone marrow, stability towards liver enzymes, and activity in the context of cell barriers, bone marrow stromal support, and short, kidney-clearance-like exposure (fig.1). The most promising compound (CCF642) emerging from this test had IC50s around 500 nM in all 8 MM cell lines tested including a proteasome inhibitor refractory line while the IC50 was not reached in 5 healthy bone marrow samples at doses up to 6750 nM. Similar sensitivity as in MM was seen in 7 lymphoma cell lines. Investigation of its mechanism of action revealed that CCF642 immediately stimulates protein ubiquitination which is followed by degradation of major myeloma survival factors (c-MYC, IRF4, NF-κB) and apoptosis, while normal bone marrow cells increase ubiquitination to a much lesser degree and only transiently without undergoing cell death. Experiments with an active biotinylated analog showed that it preferentially enters myeloma cells with cytoplasmic accumulation and over 10-fold lower entry into normal bone marrow. Immunoblots revealed that it becomes covalently attached to proteins in a time- and distribution pattern that parallels ubiquitination responses. In vitro, it bound to ubiquitin activating enzyme UBA1 at the active site cysteine in a similarly stable and reversible way as ubiquitin. Selective alkylation of cysteine sulfhydryl groups inhibited binding of biotinylated CCF642 to UBA1, while addition of ATP and ubiquitin led to its dissociation from UBA1. CCF642 may therefore at least in part act as a small molecule ubiquitin analog. Accordingly CCF642 binding to target proteins of UBA1 containing HeLa fraction II was increased by addition of ATP and blocked in the presence of EDTA. Injected twice a week IP at 30mg/kg it suppressed systemically engrafted luciferase expressing 5TGM1 mouse myeloma cells in syngeneic mice comparable to bortezomib given at the MTD for this mouse strain (0.5mg/kg SC twice a week) with equal prolongation of survival. Results support use of our “sandwich” assay to select myeloma drug candidates for in vivo testing and reveal a new UBA1 interacting small molecule ubiquitination enhancer with promise for clinical translation. Figure 1: Sandwich Three Organ System Assay Figure 1:. Sandwich Three Organ System Assay Disclosures No relevant conflicts of interest to declare.

Thrombopoietin-Induced Stimulation of Megakaryocyte- Enriched Bone Marrow Cultures

1979 ◽  
Author(s):  
K. L. Kellar ◽  
B. L. Evatt ◽  
C. R. McGrath ◽  
R. B. Ramsey
Keyword(s):  
Bone Marrow ◽  
Dna Synthesis ◽  
Bone Marrow Cells ◽  
Rabbit Plasma ◽  
Bone Marrow Cultures ◽  
Plasma Fractions ◽  
Marrow Cultures ◽  
Stimulation Of

Liquid cultures of bone marrow cells enriched for megakaryocytes were assayed for incorporation of 3H-thymidine (3H-TdR) into acid-precipitable cell digests to determine the effect of thrombopoietin on DNA synthesis. As previously described, thrombopoietin was prepared by ammonium sulfate fractionation of pooled plasma obtained from thrombocytopenic rabbits. A control fraction was prepared from normal rabbit plasma. The thrombopoietic activity of these fractions was determined in vivo with normal rabbits as assay animals and the rate of incorporation of 75Se-selenomethionine into newly formed platelets as an index of thrombopoietic activity of the infused material. Guinea pig megakaryocytes were purified using bovine serum albumin gradients. Bone marrow cultures containing 1.5-3.0x104 cells and 31%-71% megakaryocytes were incubated 18 h in modified Dulbecco’s MEM containing 10% of the concentrated plasma fractions from either thrombocytopenic or normal rabbits. In other control cultures, 0.9% NaCl was substituted for the plasma fractions. 3H-TdR incorporation was measured after cells were incubated for 3 h with 1 μCi/ml. The protein fraction containing thrombopoietin-stimulating activity caused a 25%-31% increase in 3H-TdR incorporation over that in cultures which were incubated with the similar fraction from normal plasma and a 29% increase over the activity in control cultures to which 0.9% NaCl had been added. These data suggest that thrombopoietin stimulates DNA synthesis in megakaryocytes and that this tecnique may be useful in assaying thrombopoietin in vitro.

Arrest of In Vitro T Cell Differentiation of Normal Bone Marrow‐Derived CD34+Stem Cells with Thymic Epithelial Fragments from Children with AIDS

Stem Cells ◽  
1996 ◽  
Vol 14 (5) ◽  
pp. 533-547 ◽  
Author(s):  
Margaret E. Ruiz ◽  
John Freeman ◽  
John D. Bouhasin ◽  
Alan P. Knutsen ◽  
Mary J. C. Hendrix
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Normal Bone Marrow ◽  
Normal Bone

scholarly journals 2'-Deoxycytidine protects normal human bone marrow progenitor cells in vitro against the cytotoxicity of 3'-azido-3'-deoxythymidine with preservation of antiretroviral activity

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 1923-1928 ◽  
Author(s):  
K Bhalla ◽  
M Birkhofer ◽  
GR Li ◽  
S Grant ◽  
W MacLaughlin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
High Dose ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Bone Marrow Progenitor Cells ◽  
Bone Marrow Progenitor ◽  
High Concentrations ◽  
Anti Hiv

Abstract Bone marrow cytotoxicity of 3′-azido-3′-deoxythymidine (AZT), an anti- human immunodeficiency virus (anti-HIV) drug, has been attributed to deoxyribonucleotide pool perturbations that might result in impaired DNA synthesis in normal bone marrow elements. We examined, in vitro, the effect of high, but clinically achievable and nontoxic, concentrations of 2′-deoxycytidine (dCyd) (greater than or equal to 100 mumol/L) on high-dose AZT mediated growth inhibition and intracellular biochemical perturbations in normal bone marrow progenitor cells. Colony formation by bone marrow progenitor cells in semisolid medium was significantly protected by dCyd against the inhibitory effects of co-administered, high concentrations of AZT (10 mumol/L). Also, dCyd significantly corrected AZT mediated depletion of intracellular thymidine triphosphate (dTTP) and dCyd triphosphate (dCTP) levels in normal bone marrow mononuclear cells (BMMC). Moreover, dCyd reduced the intracellular accumulation of AZT triphosphate (AZT-TP) and its DNA incorporation in BMMC. In contrast, co-administration of dCyd (100 mumol/L to 1 mmol/L) did not reverse AZT (10 mumol/L) mediated suppression of HIV infectivity in HUT-102 cells in culture, although a partial reduction in intracellular AZT-TP pools and its DNA incorporation as well as a correction of AZT mediated depletion of dTTP and dCTP pools was observed in these cells. These studies suggest that dCyd at high concentrations might ameliorate the bone marrow cytotoxicity of high-dose AZT without impairing its anti-HIV effect.

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