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

Investigating the role of bone marrow stroma in the response of haematopoietic stem cells to plasmodium berghei infection

2017 ◽  
Vol 53 ◽  
pp. S101
Author(s):  
Myriam Haltalli ◽  
Kira Glatzel ◽  
Nicola Ruivo ◽  
Andrew Blagborough ◽  
Cristina Lo Celso
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Plasmodium Berghei ◽  
Bone Marrow Stroma ◽  
Haematopoietic Stem Cells ◽  
Marrow Stroma

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.

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

Distinct osteoblastic differentiation potential of murine fetal liver and bone marrow stroma-derived mesenchymal stem cells

2008 ◽  
Vol 104 (2) ◽  
pp. 620-628 ◽  
Author(s):  
Olivia Fromigué ◽  
Zahia Hamidouche ◽  
Sébastien Chateauvieux ◽  
Pierre Charbord ◽  
Pierre J. Marie
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Fetal Liver ◽  
Osteoblastic Differentiation ◽  
Bone Marrow Stroma ◽  
Differentiation Potential ◽  
Marrow Stroma

Adipogenic Differentiation of Human Adult Stem Cells From Bone Marrow Stroma (MSCs)

2003 ◽  
Vol 19 (2) ◽  
pp. 256-264 ◽  
Author(s):  
Ichiro Sekiya ◽  
Benjamin L Larson ◽  
Jussi T Vuoristo ◽  
Jian-Guo Cui ◽  
Darwin J Prockop
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adult Stem Cells ◽  
Adipogenic Differentiation ◽  
Bone Marrow Stroma ◽  
Human Adult ◽  
Marrow Stroma

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

Osteomyelosclerosis, Anemia and Extramedullary Hematopoiesis in Mice Deficient for the Transcription Factor NFAT (Nuclear Factor of Activated T Cells) c2

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3726-3726
Author(s):  
Satu Kyttälä ◽  
Wolfgang Bauer ◽  
Michael Haase ◽  
Ivonne Habermann ◽  
Gerhard Ehninger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Extramedullary Hematopoiesis ◽  
Hematopoietic Progenitor Cells ◽  
Nuclear Factor ◽  
Bone Marrow Stroma ◽  
Hematopoietic Progenitor ◽  
Activated T Cells ◽  
Marrow Stroma

Abstract NFAT (Nuclear Factor of Activated T cells) is a family of five calcium-induced, calcineurin-dependent transcription factors, characterized as master regulators of inducible gene expression in T lymphocytes. In various tissues (including bone, cartilage and adipose tissue), NFAT factors have also been found to regulate processes of cellular adaptation and differentiation. NFAT family members are also expressed in human CD34+ hematopoietic progenitor cells as well as in mesenchymal stem cells; however, a biological function of NFAT in these cells, such as a role in hematopoietic differentiation, has not yet been described. To determine a potential role for NFAT in hematopoiesis, we characterized the steady-state hematopoiesis in NFATc2 knockout (KO) mice by analyzing peripheral blood, bone marrow and extramedullary tissue (spleen and liver) of KO and age-matched wildtype (WT) mice by cytology, histopathology as well as flow cytometry. No significant abnormalities were observed in KO mice of young age (6–12 weeks). NFATc2 KO mice of older age (>12 months), however, were found to be anemic, with a significant decrease in red blood cell counts as well as in hemoglobin and hematocrit values, and also showed decreased numbers of peripheral blood platelets as compared to the WT. In contrast, no significant differences between WT and KO were found in total counts of white blood cells or in leukocyte differentials. Femora of NFATc2 KO mice appeared macroscopically pale and, upon elutriation, gave yield to less than 50% of bone marrow cells compared to the WT, indicating bone marrow hypoplasia. Further analysis of bone marrow differentials by morphology and flow cytometry showed a profound decrease in erythroid cells as well as in megakaryocytes. Histopathological examination of KO bone marrow sections revealed evidence of bone marrow sclerosis, as indicated by an increase in bone trabeculae and osteoblasts within the marrow space. In some mice, an increase in reticulin fiber content was also noted. Interestingly, both liver and spleens of NFATc2 KO mice showed clear evidence for extramedullary hematopoiesis, suggesting that displacement of hematopoietic cells by the bone marrow stroma may be a possible cause of the observed cytopenias. These results show that NFATc2 knockout mice over their lifespan develop a phenotype, which clinically resembles human osteomyelofibrosis/-sclerosis. The underlying mechanism for the observed hematopoietic abnormalities has to be defined, in particular the respective contribution of hematopoietic and bone marrow stroma cells. Given that NFAT factors are expressed at considerable levels in both hematopoietic progenitor cells and mesenchymal stem cells, our results should encourage further studies on the yet undefined role of these transcription factors within the bone marrow hematopoietic niche.

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.

CD117 Expression May Signify Enduring Proliferative Capacity of Amniotic Fluid-Derived Mesenchymal Stem Cells (MSC).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3699-3699
Author(s):  
William K. Decker ◽  
Sufang Li ◽  
Dongxia Xing ◽  
Simon N. Robinson ◽  
Hong Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Laser Ablation ◽  
Amniotic Fluid ◽  
Cell Lines ◽  
Cellular Component ◽  
Bone Marrow Stroma ◽  
Proliferative Capacity ◽  
Marrow Stroma ◽  
Doubling Times

Abstract INTRODUCTION: Recent publications have suggested that a highly pluripotent stem cell population may be derived from the cellular fraction of amniotic fluid. During the surgical correction of twin to twin transfusion syndrome by fetoscopic laser ablation, large amounts of amniotic fluid are harvested, the cellular component of which could serve as a potentially rich source of amniotic fluid-derived pluripotent stem cells. To explore this hypothesis, we collected large amounts of amniotic fluid following fetoscopic laser ablation procedures and sought to generate and characterize amniotic fluid-derived stem cells (AFS) as described previously.1 METHODS: Amniotic fluid was collected following fetoscopic laser ablation with IRB approval. The total cellular component was cultured in α-MEM (Hyclone) supplemented with 15% ES FBS (Invitrogen), 100 U/ml penicillin G/streptomycin, 2 mM L-glutamine, 18% Chang Basal Medium, and 2% Chang C Medium (both from Irvine Scientific). Adherent cells were expanded and selected with CD117 microbeads (Miltenyi Biotec). Cells were characterized by flow cytometry, and hematologic pluripotence was assessed by culture in 100 ng/ml GM-CSF, co-culture with OP-9 cells, or co-culture with primary human bone-marrow stroma. Proliferative capacity was assessed and doubling times were determined for all serial passages. RESULTS: Amniotic fluid derived cells were typically CD90posCD105posHLA-DRneg with minority populations that were HLA-DRlow and CD133pos. This phenotype is consistent with that of bone marrow-derived MSCs. Cellular morphology was also consistent with that of bone marrow-derived MSCs. We did not detect any expression of CD34, CD45, or CD38 either pre- or post-CD117 selection. Some samples were fully devoid of CD117pos cells; however, others did exhibit CD117-expressing cells which could be selected. Attempts at transdifferentiation of either CD117pos or CD117neg cells by ES cell methods were unsuccessful; the AFS cell phenotype remained consistent throughout the addition of exogenous cytokines or co-culture with bone marrow stroma. CD117neg AFS cell lines began to divide more slowly, exhibiting doubling times of 90 hours by post-selection passage 10. In contrast, CD117pos AFS cell lines maintained a doubling time of 25–30 hours through post-selection passage 10. CONCLUSIONS: The AFS cells derived from fetoscopic laser ablation procedures exhibited an MSC phenotype and did not appear to have pluripotent plasticity. We hypothesize that AFS cells with greater plasticity might exist at the time of diagnostic amniocentesis (week 14–16) but appear to be absent in the fluid samples that we obtained on weeks 24–26. The AFS MSCs had a proliferative potential greater than that exhibited by bone marrow MSCs, and the presence of surface CD117 (SCF receptor) seemed to be predictive of an enduring proliferative ability. Further study will be necessary to determine the validity and significance of this correlation.

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