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Long-term human hematopoiesis in the SCID-hu mouse.
Brief Communication. Related Articles for " ". Acta Haematol ; To view the fulltext, please log in. To view the pdf, please log in. Here, we briefly summarized hu-or hu-leukemic-mice models in SCID strain with injection of human cells and suggest the necessity of hu-mice models in biomedical research, especially for leukemia.
However, Weissman IL group failed to show functional immune network and only presented human phenotype in PB status. Leukocytes contain rare population for stem cells, which can produce all hematopoietic cells lineages, and show severe variation in reproducing human cell engraftments Mosier et al. Because irradiation partly plays a role in frustrating murine hematopoietic cells, the irradiated condition is similar to SCID mice.
At , Lapidot T et al. Nevertheless, a disadvantage of the SCID strain found that it is the low frequency of functional immune cells. Also, engraftment efficiency is higher in human tumors or viruses rather than in human primary cells.
Human Hematopoiesis in SCID Mice
Ishikawa F et al. The completion of this model in the development of hu-mice models is remarkable proficiency. History of hu-mice model is briefly presented by Fig. AML is one of the hematologic malignancies, which occurs by immature blast accumulation with dysfunctional immune network Lion et al.
Additionally, uncontrolled blast proliferation results in abnormal hematopoietic cells in BM and PB Ferrara and Schiffer, To overcome this weakness, the hu-mice model was first applied to study AML. AML cells and human leukemic promyelocytes of the HL lines were subcutaneously injected into nude mice Palu et al. Despite the useful benefits of nude mice, it is not enough to develop a proper hu-leukemic-mice model due to vitalization of innate immune cells. Bosma et al. Because the cells were intravenously implanted into irradiated SCID mice, a model is a more preferential situation with leukemic condition.
Unlike in AML, acute lymphoid leukemia ALL patients derived from primary cells displayed high rates of engraftment, suggesting variation of model stabilization based on cell sources De Lord et al. Many attempts have been made to develop hu-leukemic-mice models with stable engraftment of human cells. Ever since embryonic rest theory was formulated in by Julius Cohnheim, stating that cancers are derived from rest embryonal cells in adult tissues, various approaches have been carried out to identify LSCs using hu-leukemic mice model.
BM is one of the representative tissues containing LSCs, which also leads to the relapse of leukemia. Recapitulated environments such as human bone fragments and BM cells were applied into SCID mice and revealed that biologic features of the leukemia guaranteed better than previously. Similar to normal hematopoietic stem cells, the frequency of leukemic stem or initiating cells is rare and most AML cells can rapidly lose their proliferative potential, when blasts free from niche.
This result strongly provides the possibility that hu-leukemic mice are only available as a model to identify bona fide LSCs. Because residual lymphocytes cannot allow engraftment of leukemic stem cells, some investigators performed irradiation to remove murine immune cells Shpitz et al. These efforts partly led to increase short-term engraftment of human cells, unfortunately, recipient murine die early on in the experimental schedule.
Thus, Bonnet D et al. Based on advanced model development without cessation, identification of LSCs and HSCs will be quickly revealed by modifying the hu-leukemic mice model.
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History of hu-mice model for leukemia study is briefly presented by Fig. Regardless of the type of the cancer, the hu-mice model should be needed to investigate tumor microenvironmental explorer. Especially, interaction between immune cells and leukemic stem cells might be optimized through the hu-leukemic-mice model.
Similar with hu-mice models, accomplishment of hu-leukemic-mice model for microenvironmental study gradually enlarged in their spectrum from vitro study to vivo model Fig. Most leukemia accompanied by an impaired immune system leads to the failure of blast suppression.
HSC-PDX Models: Valuable Tools in Immunotherapy Drug Development
Thus, immune cell modulation as a therapeutic target is an emerging issue in treating AML. Also, another arguing point is about the hierarchical relevance between malignant niche and leukemic stem cells. Recently, Boyerinas B et al. Conversely, Flach J insists that conversion of normal HSC into malignant cells occur by DNA damage, implying the importance of niche in the driving of malignant cells Flach et al.
To elucidate the controversy, an accurate interpretation could be possible through reproducible and credible vivo model, hu-leukemic-mice model. In addition, the progress of stem cell biology following the application of induced pluripotent stem cells into the clinic and regenerative medicine will elevate the usability of the hu-mice model. We briefly summarized the history of hu-mice model for immunology and pointed out the hu-disease mice model, especially for AML.
Advanced hu-leukemic-mice models will contribute to analysis of machinery of underlying AML features and immunologic interaction.
To completely treat AML, a better understanding of the immune niche and LSCs mechanism is needed and effective therapeutic protocols might be accomplished by mimicking the hu-mice system. Search for Search All Journals. Title Author Keyword Volume Vol. CrossRef 2.
Expansion of human SCID-repopulating cells under hypoxic conditions
Correspondence to: Hee-Je Kim. Received June 22, ; Accepted June 29, Abstract A humanized mice hu-mice model is extremely valuable to verify human cell activity in vivo condition and is regarded as an important tool in examining multimodal therapies and drug screening in tumor biology. Keywords : Humanized, Mice model, Acute myeloid leukemia. Development of hu-leukemic mice model AML is one of the hematologic malignancies, which occurs by immature blast accumulation with dysfunctional immune network Lion et al.
Application and perspectives of hu-leukemic mice model Regardless of the type of the cancer, the hu-mice model should be needed to investigate tumor microenvironmental explorer. Based on these, modified stem cell sources transplanted to optimize leukemia model.
The latest version of hu-mice model has a limitation to investigate relevance between microenvironmental factor such as immune cells and hematopoietic stem cells. To overcome this, notable protocol should be developed such as sequential transplantation, which first build hu-mice model with normal HSC, and then induce leukemia condition. Contribution of bone microenvironment to Leukemogenesis and leukemia progression. Bonnet, D, and Dick, JE Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.
ipdwew0030atl2.public.registeredsite.com/325372-tracking-mobile.php A severe combined immunodeficiency mutation in the mouse. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Cell Immunol. Acute myeloid leukemia in the vascular niche.