Dominique Bonnet

..This review summarizes all the recent advances made in the human HSC field and examines the impacts that these discoveries may have both clinically and in understanding the organization of the human haematopoietic system...

..This report will review our current knowledge on LSC development and finally demonstrate how these discoveries provide a paradigm for identification of CSCs from solid tumours...

..This report will review our current knowledge on normal and LSC development and examine the impact of these discoveries may have clinically and in our understanding of the leukaemogenic process...

..This report will review our current knowledge on leukemic stem cell development and finally demonstrate how these discoveries provide a paradigm for identification of Cancer Stem Cell (CSC) from solid tumors...

..We will concentrate on the model of acute myeloid leukemia, as it was the first type of leukemia for which the xenotransplantation model was developed...

..This report will review our current knowledge on leukaemic stem cells development and finally demonstrate how these discoveries provide a paradigm for identification of cancer stem cells from solid tumours...

..We also discuss the recent unexpected degree of differentiation plasticity that have been reported recently and the impacts these new discoveries may have in stem cell therapy...

..In this review, we will summarize the recent advances made in the human HSC field, and we will examine the impacts these discoveries may have clinically and on our understanding of the organization of the human hematopoietic system...

....

..Interestingly, the presence or absence of Tat in viral preparations did not influence the transduction efficiency of HIV-1 vectors in human HSCs...

..Identification and isolation of leukemic cells on the basis of ALDH activity provides a tool for their isolation and further analysis...

..A possible selection-based mechanism of stem cell pool aging is discussed...

..Our findings also provide a challenge to contemporary attempts to improve the outcome of AML using myeloid antigen-targeted therapies, given the potential for HSC killing...

..Our results suggest an important difference between leukemic initiating cells between engrafting and nonengrafting AML cases that correlates with treatment response...

..These findings might be clinically relevant for future stem cell therapy studies. Disclosure of potential conflicts of interest is found at the end of this article...

..More importantly, the work suggests that there is greater variation in the phenotypes of leukemia-initiating cells than previously suggested...

....

..Because no selective pressure is applied to retain the human genomic material, it is gradually lost over time, leading to a variable phenotype of the chimeric cells and making their detection difficult...

..Elevated levels of aldehyde dehydrogenase (ALDH) have been demonstrated in murine and human progenitor cells when compared to other hematopoietic cells...

....

..CONCLUSIONS: In our hands, murine SP cells with the expected surface immunophenotype can be identified on a MoFlo, LSR and a factory standard FACSAria...

..A general and easy protocol is presented here for isolating stromal cells from different inbred and transgenic mice commonly used in the stem cell biology field...

..The characterization of human DNGR-1+ BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy...

..Altogether we are proposing a hierarchical organization of the mesenchymal compartment, placing SSEA-1+ cells at the apex of this hierarchy...

..It is not possible to perform these experiments in humans, but xenotransplantation mouse models provide the closest paradigm for the human hematopoietic environment at the present time...

..Mesenchymal stromal cells in the bone marrow may favor the persistence and progression of leukemia by preserving the proliferation and self-renewal capacities of the malignant progenitor cells...

..These data suggest that the inhibition of aurora B kinase may be a useful therapeutic strategy in the treatment of AML and that further exploration of dosing and treatment schedules is warranted in clinical trials...

..Nevertheless, the Basic Protocol could be applied to other sorts of blood disorders...

..Hence, the SP cell fraction highlights a subset of the long-term repopulating cells found within the already highly purified KTLS fraction...

..Several issues concerning lineage commitment and inter-conversion potential between different mesenchymal cell-types are reviewed...

..We conclude that tracking of labeled cells using non-genetically encoded markers should always be accompanied by drastic cross validation using multimodality approaches...

..Here, we have focused on hematopoietic stem cells as they are one of the best-characterized adult stem cell populations, and have been extensively studied for the consequences of ageing in vivo and in vitro...

..The biology is exciting but not yet well enough understood to support therapeutic advances...

..Interestingly these studies pave the way for this technology to undergo development as a flow cell for utility as a sheathless cell most useful in flow cytometry...

..We conclude that the clinical use of MSC in conditions in which a malignant disease is involved should be handled with extreme caution...

..Identification of putative tissue stem cells would be necessary before purification strategies can be devised. In this review, we discuss the evidence for these models, and the conflicting results obtained to date...

..A 51-bp deletion was detected in CCND3 in a patient with normal karyotype AML. This validated panel now provides an important tool to evaluate other candidate genes in the genesis of myeloid malignancy...

..Xenotransplantation assays should be used wherever possible to test the suitability of candidate antigens for targeted therapy, including the assessment of the effect on normal cells...