In-vivo and in-vitro association between leukemic cells and marrow stromal cells: A murine model

1988 ◽  
Vol 12 (8) ◽  
pp. 631-636 ◽  
Author(s):  
Harinder S. Juneja ◽  
Sang Lee
Keyword(s):  
Murine Model ◽  
Stromal Cells ◽  
Marrow Stromal Cells ◽  
Leukemic Cells

Differentiation arrest and stromal cell-independent growth of murine erythroleukemia cells are associated with elevated expression of ets-related genes but not with mutation of p53

1993 ◽  
Vol 13 (9) ◽  
pp. 5582-5592
Author(s):  
R J Nibbs ◽  
K Itoh ◽  
W Ostertag ◽  
P R Harrison
Keyword(s):  
Stromal Cells ◽  
Stromal Cell ◽  
Gene Activation ◽  
Leukemic Cells ◽  
Term Survival ◽  
Elevated Expression ◽  
D Cells ◽  
Murine Erythroleukemia

The ELM erythroleukemia is novel in that long-term survival of leukemic cells in culture (ELM-D cells) is dependent on contact with a bone marrow-derived stromal feeder cell layer. However, a number of stroma-independent (ELM-I) mutants that vary in their ability to differentiate in vitro in response to erythropoietin and interleukin-3 have been derived. We have attempted to define the genetic changes responsible for these different phenotypes. At the p53 locus in the primary leukemic cells, one copy of the gene has been lost whereas the other contains an 18-bp depletion, implicating its mutation as an early step in the development of the leukemia. Changes in ets gene expression have also been found. The Fli-1 gene region is rearranged in the primary tumor because of the insertion of a retrovirus inserted upstream of one Fli-1 allele, but this does not result in Fli-1 gene activation in any of the ELM-D or ELM-I cell lines except one. It seems significant that this line is the only one to have lost the ability to differentiate in response to erythropoietin. In addition, up-regulation of erg is associated with stromal cell-independent growth, since all ELM-I mutants have moderate levels of erg mRNA, whereas only low or undetectable levels are found in primary leukemic cells in vivo or in ELM-D cells in vitro. This up-regulation of erg mRNA seems to be important for stromal cell-independent growth, since ELM-D cells show elevated expression of the erg gene after separation from stromal cells. This seems to be made permanent in ELM-I mutants, since they do not down-regulate erg mRNA when grown in contact with stromal cells. We therefore propose that ets family members regulate both the survival and differentiation of erythroid cells.

p38MAPK Inhibitor LSN2322600 Modulates the Bone Marrow Microenvironment and Inhibits Osteoclastogenesis in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5042-5042
Author(s):  
Kenji Ishitsuka ◽  
Teru Hideshima ◽  
Paola Neri ◽  
Sonia Vallet ◽  
Norihiko Shiraishi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Mononuclear Cells ◽  
Severe Combined Immunodeficiency ◽  
Marrow Stromal Cells ◽  
Skeletal Complications

Abstract The interaction between multiple myeloma (MM) cells and the bone marrow (BM) microenvironment plays a crucial role not only in proliferation and survival of MM cells, but also in osteoclastogenesis. In this study, we examined diverse potential of novel p38MAPK inhibitor LSN2322600 (LSN) for MM therapy in vitro and in vivo. The cytotoxic activity of LSN against MM cell lines was modest; however, LSN significantly enhances the cytotoxicity of Bortezomib by down-regulating Bortezomib-induced heat shock protein (HSP) 27 phosphorylation. We next examined the effects of LSN on cytokine secretion in MM cells, bone marrow stromal cells and osteoclast precursor cells. LSN inhibited IL-6 secretion from long-term cultured-bone marrow stromal cells (LT-BMSCs) and bone marrow mononuclear cells (BMMNCs) from MM patients in remission. LSN also inhibited MIP-1 α secretion by fresh tumor cells, BMMNCs and CD14 positive cells. Since these cytokines mediate osteoclastogenesis, we further examined whether LSN could inhibit osteoclastogenesis. Importantly, LSN inhibited in vitro osteoclastogenesis induced by macrophage-colony stimulating factor (M-CSF) and soluble receptor activator of nuclear factor- κ B ligand (sRANKL), as well as osteoclastogenesis in the severe combined immunodeficiency (SCID)-Hu mouse model of human MM. These results suggest that LSN represents a promising novel targeted strategy to reduce skeletal complications as well as to sensitize or overcome resistance to Bortezomib.

45 DEVELOPMENT OF BOVINE NUCLEAR TRANSFER EMBRYOS DERIVED FROM ADULT MARROW STROMAL CELLS AND FETAL MUSCLE CELLS

2009 ◽  
Vol 21 (1) ◽  
pp. 122
Author(s):  
M. Murakami ◽  
X. J. Bai ◽  
W. S. Shi ◽  
W. M. Wang ◽  
W. Liu ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Donor Cell ◽  
Muscle Cells ◽  
Marrow Stromal Cells ◽  
Developmental Potential ◽  
Development In Vitro ◽  
Adult Mscs ◽  
Fetal Muscle

The use of less differentiated cells, such as marrow stromal cells (MSCs), as the nuclear donor may increase the efficiencies of somatic cell cloning in cattle. Healthy offspring was produced from bovine MSCs (Kato et al. 2004 Biol. Reprod. 70, 415–418); however, there is little information that directly compared the post-implantation survival among the clones originated from MSCs and other somatic cells. The objective of this study was to evaluate the developmental potential in vitro and in vivo of bovine NT embryos derived from adult MSCs and fetal muscle cells (FMCs). Primary cell populations of MSCs and FMCs were obtained from the femurs of 8- and 12-months-old Holstein cows (MSC1 and MSC2 groups, respectively) and a Holstein fetus at 8 months of gestation (FMC group), respectively. They were used as donor cells for the NT procedure (Murakami et al. 2005 Cloning Stem Cells 7, 77–81) at passages 1 to 3. Briefly, oocytes collected from cow ovaries were enucleated at 20 h post-in vitro maturation (IVM), and the donor cell was placed into the perivitelline space. The couplets were fused electrically, activated (10 μg mL–1 cycloheximide; 4 h), and cultured in CR1aa medium. Development in vitro of these embryos is summarized in Table 1. Data were analyzed by ANOVA. The fusion rates were higher in the MSC groups than in the FMC group. The rate of cleaved embryos was significantly lower (P < 0.05) in the MSC1 group than in the other groups. However, there were no significant differences among the groups in the rates of development into morulae/blastocysts on Day 6. A total of 8 and 3 fresh good quality Day 6 embryos in the MSC1 and FMC groups, respectively, were nonsurgically transferred to 6 naturally cycling Holstein females 6 days after estrus (3 recipients/group, 1–3 embryos/female). On Day 30 of gestation, none of the recipients were pregnant in the FMC group, while 2 recipients in the MSC1 group were diagnosed as pregnant via ultrasonography; they remained pregnant on Day 80 of gestation. In addition, a total of 4 Day 7 embryos cryopreserved in 1.8 m ethylene glycol plus 0.05 m trehalose were directly transferred to 4 synchronized recipients after thawing (1 embryo/female) in the MSC1 group. Of those, 2 females were pregnant on day 30 of gestation. These results indicate that the developmental potential in vitro of bovine NT embryos derived from adult MSCs was comparable to that of the embryos derived from fetal muscle cells, and that pregnancies were produced after transfer of the fresh and frozen–thawed NT embryos derived from the MSC, but the sample size was small. Further studies with more replicates are needed to evaluate viability in vivo of these cloned embryos for comparative purposes. Table 1.Development in vitro of bovine NT embryos derived from different cell types

scholarly journals Myeloablation with diaziquone: in vitro assessment

Blood ◽  
1987 ◽  
Vol 69 (6) ◽  
pp. 1747-1752 ◽  
Author(s):  
BH Kushner ◽  
S Siena ◽  
H Castro-Malaspina
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Antineoplastic Agent ◽  
Marrow Stromal Cells ◽  
Drug Induced ◽  
In Vitro Assessment ◽  
Noxious Effect

Abstract The promising antineoplastic agent diaziquone is associated with prolonged aplasia and rare instances of bone marrow necrosis, but only mild extramedullary toxicity. To explore the drug's potential as a myeloablative agent prior to bone marrow transplantation, we compared its effects on hematopoietic versus marrow stromal cells. After short- term (one to six hours) or prolonged (three to seven days) exposure to the drug, marrow was assayed for hematopoietic (CFU-Mix, BFU-E, CFU-GM) and stromal (CFU-F) colony-forming cells and studied in long-term marrow culture (LTMC). One- and three-hour treatments produced little cytotoxicity, even at 5000 ng/mL. After six-hour treatments with this dose, marrow was depleted of CFU-Mix, BFU-E, and CFU-GM, but produced CFU-GM in LTMCs, indicating an ongoing input of CFU-GM from a surviving pre-CFU-Mix population. In contrast, elimination of the latter may be inferred from the absence of CFU-GM in LTMCs exposed for three to seven days to diaziquone at only 150 ng/mL. Under these conditions, CFU-F recovery was 40% and adherent stromal layers in LTMCs were similar to untreated controls regarding rate of development and cellular composition. Our in vitro pre-CFU-Mix-ablative regimen correlates with clinical data that show prolonged but reversible myelosuppression at steady-state diaziquone plasma levels of 101 +/- 10 ng/mL (mean +/- standard error of mean) during 7-day constant infusions. In conclusion: hematopoietic cells are more sensitive than marrow stromal cells to the dose- and highly time-dependent cytotoxicity of diaziquone, a direct drug-induced noxious effect on the marrow microenvironment is an unlikely cause of the isolated episodes of marrow necrosis after the use of diaziquone in vivo, and prolonged infusion of diaziquone represents an attractive means for achieving myeloablation in selected clinical situations.

scholarly journals Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Jack M. Milwid ◽  
Takaharu Ichimura ◽  
Matthew Li ◽  
Yunxin Jiao ◽  
Jungwoo Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Kidney Injury ◽  
Standard Of Care ◽  
Marrow Stromal Cells ◽  
Secreted Factors

Acute kidney injury is a devastating syndrome that afflicts over 2,000,000 people in the US per year, with an associated mortality of greater than 70% in severe cases. Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease. Many groups have explored the use of bone marrow stromal cells (BMSCs) for the treatment of AKI because BMSCs have been shown to possess unique anti-inflammatory, cytoprotective, and regenerative propertiesin vitroandin vivo. It is yet unresolved whether the primary mechanisms controlling BMSC therapy in AKI depend on direct cell infusion, or whether BMSC-secreted factors alone are sufficient for mitigating the injury. Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI. We observed that when BMSC-conditioned medium (BMSC-CM) is administered intravenously, it prevents tubular apoptosis and necrosis and ameliorates AKI. In addition, we observed that BMSC-CM causes IL-10 upregulation in treated animals, which is important to animal survival and protection of the kidney. In all, these results demonstrate that BMSC-secreted factors are capable of providing support without cell transplantation, and the IL-10 increase seen in BMSC-CM-treated animals correlates with attenuation of severe AKI.

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