Improved T and B cell recovery by the transfer of slowly dividing human hematopoietic stem cells

Vitacolonna, Mario; Schubert, Mario; Herbert, Nicolás; Taubert, Isabel; Singh, Rajesh; Ho, Anthony D.; Zöller, Margot

doi:10.1016/j.leukres.2009.10.015

Cited by 9 publications

(7 citation statements)

References 52 publications

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“…Other authors have shown that, in analogy to normal HSC, LSC have comparable slow divisional kinetics and the ability for extensive self‐renewal 29, 30. We and others have reported that a slow dividing fraction (PKH bright ) of HSC is superior to a fast dividing fraction (PKH dim ) in reconstituting the NOD/SCID mouse not only with myeloid cells, but also T cells and B cells 27, 31…”

Section: Divisional Kinetics and Aldh Activity Of Normal And Leukemiamentioning

confidence: 95%

“…Schubert et al have demonstrated that in the NOD/SCID mouse model, repopulating human AML initiating cells were recovered from ALDH bright as well as from slow dividing (PKH bright ) cells 27. Divisional kinetics was determined by the membrane dye (PKH) dilution method, as described previously by our group and other authors 31, 38. Comparing all these methods for enrichment of LSC candidates, we found that isolation using ALDH activity, either alone or in combination with CD34 expression, yielded comparable results according to functional parameters.…”

Section: Divisional Kinetics and Aldh Activity Of Normal And Leukemiamentioning

confidence: 99%

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Liver fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet-induced nonalcoholic fatty liver disease

et al. 2013

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Activation of hepatic stellate cells (HSCs) is crucial to the development of fibrosis in nonalcoholic fatty liver disease. Quiescent HSCs contain lipid droplets (LDs), whose depletion upon activation induces a fibrogenic gene program. Here we show that liver fatty acid-binding protein (L-Fabp), an abundant cytosolic protein that modulates fatty acid (FA) metabolism in enterocytes and hepatocytes also modulates HSC FA utilization and in turn regulates the fibrogenic program. L-Fabp expression decreased 10-fold following HSC activation, concomitant with depletion of LDs. Primary HSCs isolated from L-FABP−/− mice contain fewer LDs than wild type (WT) HSCs, and exhibit upregulated expression of genes involved in HSC activation. Adenoviral L-Fabp transduction inhibited activation of passaged WT HSCs and increased both the expression of prolipogenic genes and also augmented intracellular lipid accumulation, including triglyceride and FA, predominantly palmitate. Freshly isolated HSCs from L-FABP−/− mice correspondingly exhibited decreased palmitate in the free FA pool. To investigate whether L-FABP deletion promotes HSC activation in vivo, we fed L-FABP−/− and WT mice a high fat diet supplemented with trans-fatty acids and fructose (TFF). TFF-fed L-FABP−/− mice exhibited reduced hepatic steatosis along with decreased LD abundance and size compared to WT mice. In addition, TFF-fed L-FABP−/− mice exhibited decreased hepatic fibrosis, with reduced expression of fibrogenic genes, compared to WT mice. Conclusion L-FABP deletion attenuates both diet-induced hepatic steatosis and fibrogenesis, despite the observation that L-Fabp paradoxically promotes FA and LD accumulation and inhibits HSC activation in vitro. These findings highlight the importance of cell-specific modulation of hepatic lipid metabolism in promoting fibrogenesis in nonalcoholic fatty liver disease.

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Section: Divisional Kinetics and Aldh Activity Of Normal And Leukemiamentioning

confidence: 95%

Section: Divisional Kinetics and Aldh Activity Of Normal And Leukemiamentioning

confidence: 99%

Liver fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet-induced nonalcoholic fatty liver disease

et al. 2013

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“…27 Divisional kinetics was determined by the membrane dye (PKH) dilution method, as described previously by our group and other authors. 31,38 Comparing all these methods for enrichment of LSC candidates, we found that isolation using ALDH activity, either alone or in combination with CD34 expression, yielded comparable results according to functional parameters. The efficiency of isolation of viable ALDH bright cells for functional experiments was, however, consistently higher than using other methods.…”

Section: Cd38mentioning

confidence: 97%

“…29,30 We and others have reported that a slow dividing fraction (PKH bright ) of HSC is superior to a fast dividing fraction (PKH dim ) in reconstituting the NOD/SCID mouse not only with myeloid cells, but also T cells and B cells. 27,31 In preliminary experiments, we attempted to isolate LSC based on slow divisional kinetics using dilution of PKH membrane dye or dilution of cytosolic carboxyfluorescein succinimidyl ester (CFSE) dye during divisions as a parameter. With this technology, we were able to isolate a very limited number of leukemia cells that fulfilled some of the criteria for LSC candidates.…”

Section: Divisional Kinetics and Aldh Activity Of Normal And Leukemiamentioning

confidence: 99%

Leukemia stem cells

Buss

2011

Intl Journal of Cancer

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Leukemia stem cells (LSCs) might originate from malignant transformation of normal hematopoietic stem cells (HSCs), or alternatively, of progenitors in which the acquired mutations have re-installed a dysregulated self-renewal program. LSCs are on top of a hierarchy and generate leukemia cells with more differentiated characteristics. While most leukemia cells are initially sensitive to chemo-and radiotherapy, LSCs are resistant and are considered to be the basis for disease relapse after initial response. Albeit important knowledge on LSC biology has been gained from xenogeneic transplantation models introducing human leukemia cells into immune deficient mouse models, the prospective identification and isolation of human LSC candidates has remained elusive and their prognostic and therapeutic significance controversial. This review focuses on the identification, enrichment and characterization of human LSC derived from patients with acute myeloid leukemia (AML). Experimental data demonstrating the clinical significance of estimating LSC burden and strategies to eliminate LSC will be summarized. For long-term cure of AML, it is of importance to define LSC candidates and to understand their tumor biology compared to normal HSCs. Such comparative studies might provide novel markers for the identification of LSC and for the development of treatment strategies that might be able to eradicate them.

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“…Firstly, it is needed to put MSCs on the same footing as HSCs, in which the in vivo phenotype is well established [93] allowing the direct study of the function of uncultured HSCs in animal models [94]. Secondly, if the phenotype of plastic-adherent culture-initiating MSCs was known, the contribution of other adherent cells from the marrow (hematopoietic progenitors, monocytic-, and endothelial-lineage cells) to MSC “plasticity” and other characteristics would have been much clearer.…”

Section: Markers For Prospective Isolation Of Bm Mscs In Humans Anmentioning

confidence: 99%

Markers for Characterization of Bone Marrow Multipotential Stromal Cells

Boxall

Jones

2012

Stem Cells International

244

187

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Given the observed efficacy of culture-expanded multipotential stromal cells, also termed mesenchymal stem cells (MSCs), in the treatment of graft-versus host and cardiac disease, it remains surprising that purity and potency characterization of manufactured cell batches remains rather basic. In this paper, we will initially discuss surface and molecular markers that were proposed to serve as the indicators of the MSC potency, in terms of their proliferative potential or the ability to differentiate into desired lineages. The second part of this paper will be dedicated to a critical discussion of surface markers of uncultured (i.e., native) bone marrow (BM) MSCs. Although no formal consensus has yet been reached on which markers may be best suited for prospective BM MSC isolation, markers that cross-react with MSCs of animal models (such as CD271 and W8-B2/MSCA-1) may have the strongest translational value. Whereas small animal models are needed to discover thein vivofunction on these markers, large animal models are required for safety and efficacy testing of isolated MSCs, particularly in the field of bone and cartilage tissue engineering.

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Improved T and B cell recovery by the transfer of slowly dividing human hematopoietic stem cells

Cited by 9 publications

References 52 publications

Liver fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet-induced nonalcoholic fatty liver disease

Liver fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet-induced nonalcoholic fatty liver disease

Leukemia stem cells

Markers for Characterization of Bone Marrow Multipotential Stromal Cells

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