Chromatin-modifying agents permit human hematopoietic stem cells to undergo multiple cell divisions while retaining their repopulating potential

Araki, Hiroto; Yoshinaga, Kazumi; Boccuni, Piernicola; Zhao, Yan; Hoffman, Ronald; Mahmud, Nadim

doi:10.1182/blood-2006-07-035287

Cited by 96 publications

(118 citation statements)

References 60 publications

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“…CD90 (Thy-1) is a 25-to 37-kDa cell-surface-anchored glycoprotein (Rege and Hagood, 2006). Its expression has been found in bone marrowderived mesenchymal stem cells (Dennis et al, 2007), hepatic stem/progenitor cells (La´zaro et al, 2003;Dan et al, 2006;Herrera et al, 2006), hematopoietic stem cells and keratinocytic stem cells (Nakamura et al, 2006;Araki et al, 2007;Haack-Sorensen et al, 2007). It has also been identified in human liver CSCs, murine breast CSCs and primarily cultured CD133 þ glioblastoma CSCs (Liu et al, 2006;Cho et al, 2008;Yang et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

et al. 2011

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Identification and characterization of cancer stem cells (CSCs) in gastric cancer are difficult owing to the lack of specific markers and consensus methods. In this study, we show that cells with the CD90 surface marker in gastric tumors could be enriched under non-adherent, serumfree and sphere-forming conditions. These CD90 þ cells possess a higher ability to initiate tumor in vivo and could re-establish the cellular hierarchy of tumors from singlecell implantation, demonstrating their self-renewal properties. Interestingly, higher proportion of CD90 þ cells correlates with higher in vivo tumorigenicity of gastric primary tumor models. In addition, it was found that ERBB2 was overexpressed in about 25% of the gastric primary tumor models, which correlates with the higher level of CD90 expression in these tumors. Trastuzumab (humanized anti-ERBB2 antibody) treatment of hightumorigenic gastric primary tumor models could reduce the CD90 þ population in tumor mass and suppress tumor growth when combined with traditional chemotherapy. Moreover, tumorigenicity of tumor cells could also be suppressed when trastuzumab treatment starts at the same time as cell implantation. Therefore, we have identified a CSC population in gastric primary tumors characterized by their CD90 phenotype. The finding that trastuzumab targets the CSC population in gastric tumors suggests that ERBB2 signaling has a role in maintaining CSC populations, thus contributing to carcinogenesis and tumor invasion. In conclusion, the results from this study provide new insights into the gastric tumorigenic process and offer potential implications for the development of anticancer drugs as well as therapeutic treatment of gastric cancers.

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Section: Introductionmentioning

confidence: 99%

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

et al. 2011

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“…Regarding CD90 expression, more than 50% of the primary cells in Medium D and Medium M tested positive for this marker, whereas this population only accounted for about 25% of the primary cells grown in Medium DB. These CD90 + cells were considered as contaminant cells in the breast carcinoma primary culture (Araki et al, 2007;HaackSorensen et al, 2008;Nakamura et al, 2006). In sum, a marked contrast was observed with respect to the proportion of contaminant cells versus cells with the BCSC phenotype (CD44 + CD24 -and CD49f + ) in primary cultures grown in Medium DB and Medium M.…”

Section: Discussionmentioning

confidence: 99%

Optimization of culture medium for the isolation and propagation of human breast cancer cells from primary tumour biopsies

Vu¹,

Le²,

Phan³

et al. 2015

Biomed Res Ther

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Abstract-Breast cancer cells from patients hold an important role in antigen production for immunotherapy, drug testing, and cancer stem cell studies. To date, although many studies have been conducted to develop protocols for the isolation and culture of breast cancer cells from tumour biopsies, the efficiencies of these protocols remain low. This study aimed to identify a suitable medium for the isolation and propagation of primary breast cancer cells from breast tumour biopsies. Breast tumour biopsies were obtained from hospitals after all patients had given their written informed consent and were cultured according to the expanding tumour method in 3 different media: DMEM/F12 (Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12) supplemented with 10% FBS (Fetal bovine serum) and 1% antibiotic-antimycotic (Medium D); Medium 171 supplemented with 1X MEGS (Mammary Epithelial Growth Supplement) and 1% antibiotic-antimycotic (Medium M); or a 1:1 mixture of Medium D and Medium M (Medium DB). The cell culture efficiency was evaluated by several criteria, including the time of cell appearance, cell morphology, capability of proliferation, cell surface marker expression, ALDH (Aldehyde dehydrogenases) activity, karyotype, and tumour formation capacity in immune-deficient mice. Notably, primary cancer cells cultured in Medium DB showed a high expression of breast cancer stem cell surface markers (including CD44 + CD24 -and CD49f + ), low expression of stromal cell surface markers (CD90), high ALDH activity, an abnormal karyotype, and high tumour formation capacity in immune-deficient mice. These findings suggested that Medium DB was suitable to support the survival and proliferation of primary breast cancer cells as well as to enrich breast cancer stem cells.

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“…The same research team subsequently reported that the addition of 5azaD/TSA and a combination of cytokines to human cord blood CD341 cell culture also resulted in significant HSPC expansion, with CD341CD901, CFU-mix, CAFC, and SRC numbers expanded 12.5-fold, 9.8-fold, 11.5-fold, and 9.6-fold, respectively [56]. Although the mechanism of 5azaD/TSA in HSPCs expansion is still under investigation, recent studies showed that the expression of several HSC self-renewal genes and their products were up-regulated in the cells treated with 5azaD/TSA [57]. In addition, HOX-B4 expression determined by western blot was significantly higher in the cells treated with 5azaD/TSA than that observed in cells exposed to only cytokines.…”

Section: Chromatin-modifying Agentsmentioning

confidence: 99%

Expansion of hematopoietic stem/progenitor cells

Deng

Duan

2008

American J Hematol

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Hematopoietic stem/progenitor cells (HSPCs) transplantation is hampered by the low number of stem cells per sample. To tackle this obstacle, several protocols for expansion of HSPCs in vitro are currently in development, such as the use of cytokine cocktails, coculture with mesenchymal stem cells as feeder cells, and cell culture in bioreactors. With the progress in the understanding of the molecular and cellular mechanisms regulating HSPCs maintenance and expansion, more recent approaches have involved transcription regulation, cell cycle regulation, telomerase regulation, and chromatin-modifying agents. The potential clinical application and safety issues relevant to the expanded HSPCs are also discussed in this review. Am. J. Hematol. 83:922-926, 2008. V

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Chromatin-modifying agents permit human hematopoietic stem cells to undergo multiple cell divisions while retaining their repopulating potential

Cited by 96 publications

References 60 publications

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

Optimization of culture medium for the isolation and propagation of human breast cancer cells from primary tumour biopsies

Expansion of hematopoietic stem/progenitor cells

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