Role of the bone marrow stroma in the hybrid resistance phenomenon

1979 ◽  
Vol 87 (4) ◽  
pp. 343-346
Author(s):  
I. L. Chertkov ◽  
O. A. Gurevich ◽  
G. A. Udalov
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Stroma ◽  
Hybrid Resistance ◽  
Marrow Stroma

The Role of Bone Marrow Stroma in the Response of Haematopoietic Stem Cells to Plasmodium Infection

2018 ◽  
Vol 64 ◽  
pp. S70
Author(s):  
Myriam Haltalli ◽  
Kira Glatzel ◽  
Sam Watcham ◽  
Alexander Lipien ◽  
Sara Gonzalez Anton ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Stroma ◽  
Plasmodium Infection ◽  
Haematopoietic Stem Cells ◽  
Marrow Stroma

scholarly journals Role of Wnt/β-Catenin Signalling in Acute Myeloid Leukemia (AML) Cell Response to Chemotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2753-2753 ◽  
Author(s):  
Paul Takam Kamga ◽  
Adriana Cassaro ◽  
Giada Dal Collo ◽  
Annalisa Adamo ◽  
Alessandro Gatti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Critical Role ◽  
In Silico Analysis ◽  
Wnt Signalling ◽  
Bone Marrow Stroma ◽  
Response To Chemotherapy ◽  
Marrow Stroma ◽  
Wnt Inhibitors

Abstract Background: Growing evidences from both preclinical and clinical investigations reveal the critical role of Wnt signalling for the development of many cancers and for their response to chemotherapy. Although recent studies suggest that aberrant Wnt signalling can be involved in the neoplastic myeloid cell growth, the contribution of the Wnt/β-catenin pathway to AML survival and chemoresistance is still unclear. Aims: In this study, we investigated the contribution of WNT/β-CATENIN signalling to AML survival and chemoresistance. For this purpose we tested different modulators of Wnt/β-Catenin pathway for their ability to influence AML cells proliferation and response to Cytarabine (Ara-C) or Idarubicin treatment. Methods: AML primary blast cells(30 samples) or AML cell lines cultured alone or in presence of human bone marrow mesenchymal stromal cells (hBM-MSCs), were treated with with Cytarabine (Ara-C) or Idarubicin, in presence or absence of Wnt modulators, including ligands (Wnt3a, Wnt5a/5b), Porcupine inhibitors (IWP-2), LRP6 inhibitors (Niclosamide), or antagonists of TCF/β-catenin (PKF118-310, PNU-74654). Results: In silico analysis showed the enrichment of Wnt signalling components in AML samples. Western Blot and flow cytometry showed the presence of total β-catenin only in about 2/3 of primary samples analyzed, while . β-catenin positive samples had different degree of activation of the pathway, as revealed by the expression of active forms of β-catenin, including (Ser675)β-catenin and non-phospho-(Ser33/37/Thr41) β-catenin. Notably, we found that active forms of β-catenin increased in AML samples in co-culture with hBM-MSCs, thus suggesting that Wnt signalling could be involved in the crosstalk between bone marrow stroma and AML cells. The addition of Wnt or pharmacological inhibitors, such as IWP-2, PNU-74654 and Niclosamide, to the culture medium of β-catenin-positive AML samples, either cultured alone or in co-culture with hBM-MSCs, reduced AML cell proliferation with slight effect on cell death. When associated to Idarubicin, all Wnt inhibitors except IWP-2 synergycally induced a dramatic cell death in AML cells in both culture conditions. However, when Idarubicin was replaced by Ara-C the synergism was observed only with Niclosamide and PKF. Cell death was mainly due to apoptosis, as shown by Annexin-V staining. Conclusion: Overall our data show that Wnt inhibitors reduce proliferation and chemoresistance of AML cells in culture or co-culture with bone marrow stroma cells. Wnt/β-catenin signalling may represent a potential therapeutic strategy to improve AML treatment, overcoming bone marrow stromal-mediated anti-apoptotic and chemoresistance effects. Disclosures Bonifacio: Ariad Pharmaceuticals: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding; Amgen: Consultancy.

IGF Binding Protein 2 Supports the Cycling of Hematopoietic Stem Cells.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1604-1604
Author(s):  
HoangDinh Huynh ◽  
Junke Zheng ◽  
Chengcheng Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Ex Vivo ◽  
Bone Marrow Stroma ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
C Terminus ◽  
Marrow Stroma ◽  
Igf Signaling

Abstract Abstract 1604 Previously we identified IGFBP2 as an extrinsic factor that supports ex vivo expansion of hematopoietic stem cells (HSCs). The role of IGFBP2 in HSCs and cancer is very intriguing. IGFBP2 can bind to insulin-like growth factor (IGF) ligands and displays IGF-dependent growth inhibitory effects on many cell types. On the other hand, IGFBP2 is capable of stimulating growth of certain cancer cells, and is overexpressed in many cancer patients and its expression is correlated with cancer progression. Here we sought to study the role of IGFBP2 in regulation of the activity of normal HSCs. We showed that IGFBP2 was expressed in differentiated hematopoietic cells and bone marrow stroma but not in HSCs. Consistent with its gene expression pattern, IGFBP2-/- HSCs had similar repopulation activity as their wild-type counterparts. By contrast, when we transplanted HSCs into IGFBP2-/- or wild-type recipient mice, we found decreased in vivo repopulation of HSCs in primary and secondary transplanted IGFBP2-/- recipients, suggesting that the environmental IGFBP2 positively supports HSC activity. Further co-culture of HSCs with IGFBP2-/- or wild-type bone marrow stromal cells indicated that IGFBP2 produced by bone marrow stroma indeed supports HSC expansion. Consistently, HSCs in IGFBP2-/- mice showed decreased frequency and cell cycling, and had upregulated expression of cell cycle inhibitors of p21, p16, and p19. To determine whether IGFBP2's effect on HSCs depends on IGF signaling, we compared the repopulation of donor cells deficient for the IGF type I receptor in wild-type and IGFBP2-/- recipients. These HSCs that are defective in IGF signaling still have decreased repopulation in IGFBP2-/- recipients, suggesting that the environmental effect of IGFBP2 on HSCs is independent of IGF signaling. To identify the functional domain of IGFBP2 in regulation of HSC activity, we constructed IGFBP2 with mutated RGD domain or deleted c-terminus and used the mutant IGFBP2 proteins in ex vivo culture of HSCs. We found that the c-terminus of IGFBP2 is essential to support HSC activity. We are currently in the process of identifying the potential receptor of IGFBP2 on HSCs. In summary, we found that IGFBP2 supports the cycling of normal HSCs, and this effect is independent of IGF signaling. Our study is important in revealing the relationship among environmental cues and cell fates of stem cells and opens up a new avenue in investigation of the roles of IGFBP2 in stem cells and cancer. Disclosures: No relevant conflicts of interest to declare.

ROLE OF THE BONE MARROW STROMA IN ALTERING MYELOPOIESIS FOLLOWING ACUTE HYPOXIA.

Shock ◽  
1995 ◽  
Vol 3 ◽  
pp. 35
Author(s):  
R. Taneja ◽  
P. Rameshwar ◽  
M. T. Wang ◽  
J. S. Upperman ◽  
D. H. Livingston
Keyword(s):  
Bone Marrow ◽  
Acute Hypoxia ◽  
Bone Marrow Stroma ◽  
Marrow Stroma

scholarly journals Stromal colony-stimulating activity production and myeloid colony- forming cells in human hemopoietic and nonhemopoietic bone marrow

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 771-780
Author(s):  
RS Schwartz ◽  
PL Greenberg
Keyword(s):  
Bone Marrow ◽  
Cancellous Bone ◽  
Stromal Cells ◽  
Concentration Gradient ◽  
Long Bone ◽  
Bone Marrow Stroma ◽  
Colony Stimulating Activity ◽  
Marrow Stroma

In order to evaluate the role of the stromal bone marrow microenvironment in regulating granulopoiesis, we have examined the capacity of adult human proximal hemopoietic (PH) and distal nonhemopoietic (DNH) long bone to produce colony-stimulating activity (CSA), characterized the cellular sources of CSA, and quantitated the colony-forming cells (CFU-GM) of marrow from these sites. Stromal elements were obtained from slices of cancellous bone. PH bone marrow stroma contained CFU-GM concentrations similar to aspirated PH marrow and significantly more CFU-GM than DNH bone marrow: 20.7 +/- 4.8/10(5) cells and 25.8 +/- 12.0/mg bone versus 0.81 +/- 0.34/10(5) cells and 0.02 +/- 0.01/mg bone (p less than 0.001). Conditioned media prepared from PH and DNH bone were quantitated for CSA by their ability to promote in vitro granulocyte colony formation of nonadherent human marrow cells. Stromal CSA production was destroyed by freeze--thawing and was radioresistant (4400 rad). Of DNH stromal cells, 15%--30% were monocyte-macrophage, but the slow absolute numbers of these cells suggested alternative CSA cellular sources in distal bones. PH stroma produced significantly more CSA than DNH bone stroma: 0.72 +/- 0.10 versus 0.30 +/- 0.06 U/mg bone (p less than 0.01). The CSA concentration gradient between PH and DNH bones may contribute to the regulation of granulopoiesis in marrow and to the absence of hemopoiesis distally.

scholarly journals Stromal colony-stimulating activity production and myeloid colony- forming cells in human hemopoietic and nonhemopoietic bone marrow

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 771-780 ◽  
Author(s):  
RS Schwartz ◽  
PL Greenberg
Keyword(s):  
Bone Marrow ◽  
Cancellous Bone ◽  
Stromal Cells ◽  
Concentration Gradient ◽  
Long Bone ◽  
Bone Marrow Stroma ◽  
Colony Stimulating Activity ◽  
Marrow Stroma

Abstract In order to evaluate the role of the stromal bone marrow microenvironment in regulating granulopoiesis, we have examined the capacity of adult human proximal hemopoietic (PH) and distal nonhemopoietic (DNH) long bone to produce colony-stimulating activity (CSA), characterized the cellular sources of CSA, and quantitated the colony-forming cells (CFU-GM) of marrow from these sites. Stromal elements were obtained from slices of cancellous bone. PH bone marrow stroma contained CFU-GM concentrations similar to aspirated PH marrow and significantly more CFU-GM than DNH bone marrow: 20.7 +/- 4.8/10(5) cells and 25.8 +/- 12.0/mg bone versus 0.81 +/- 0.34/10(5) cells and 0.02 +/- 0.01/mg bone (p less than 0.001). Conditioned media prepared from PH and DNH bone were quantitated for CSA by their ability to promote in vitro granulocyte colony formation of nonadherent human marrow cells. Stromal CSA production was destroyed by freeze--thawing and was radioresistant (4400 rad). Of DNH stromal cells, 15%--30% were monocyte-macrophage, but the slow absolute numbers of these cells suggested alternative CSA cellular sources in distal bones. PH stroma produced significantly more CSA than DNH bone stroma: 0.72 +/- 0.10 versus 0.30 +/- 0.06 U/mg bone (p less than 0.01). The CSA concentration gradient between PH and DNH bones may contribute to the regulation of granulopoiesis in marrow and to the absence of hemopoiesis distally.

Effects of hypoxia on granulocytic-monocytic progenitors in rats. Role of bone marrow stroma

2000 ◽  
Vol 64 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Rashmi Taneja ◽  
Pranela Rameshwar ◽  
Jeffrey Upperman ◽  
Ming T. Wang ◽  
David H. Livingston
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Stroma ◽  
Marrow Stroma

scholarly journals Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma.

1992 ◽  
Vol 90 (2) ◽  
pp. 358-367 ◽  
Author(s):  
J Teixidó ◽  
M E Hemler ◽  
J S Greenberger ◽  
P Anklesaria
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Stroma ◽  
Marrow Stroma ◽  
Beta 2

ROLE OF THE BONE MARROW STROMA IN ALTERING MYELOPOIESIS FOLLOWING ACUTE HYPOXIA

Shock ◽  
1995 ◽  
Vol 3 (6) ◽  
pp. 35
Author(s):  
R. Taneja ◽  
P. Rameshwar ◽  
M. T. Wang ◽  
J. S. Upperman ◽  
D. H. Livingston
Keyword(s):  
Bone Marrow ◽  
Acute Hypoxia ◽  
Bone Marrow Stroma ◽  
Marrow Stroma
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