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  • Stem cell technology and engineering for cancer treatment

    Stem cell technology and engineering for cancer treatment

    Stem cell technology and engineering for cancer treatment

    Article · June 2015
    DOI: 10.7603/s40730-015-0013-1

    Phuc Van Pham
    Ho Chi Minh City University of Science

    Abstract

    Stem cells are not only widely used for regenerative medicine, but are also considered as a useful tool for cancer treatment. For a long time, stem cells have been utilized to renew the immune system for radiation or chemotherapy treated patients. Recently, stem cells are being engineered to carry therapeutic reagents to target tumor sites. Cancer vaccines based on the knowledge of cancer stem cells have been studied and applied for cancer treatment. Induced pluripotent stem cells have been used to create active T cells to support cancer immunotherapy. Those are due to the unique characteristics of stem cells, such as immunological tolerance, migration, and tissue repa-ration. This review discusses stem cell applications in transplantation, stem cell-based carriers, induced-pluripotent stem cells, cancer stem cells, and potential of stem cells engineering to revolutionize cancer treatment.

  • In vitro spontaneous differentiation of human breast cancer stem cells and methods to control this p

    In vitro spontaneous differentiation of human breast cancer stem cells and methods to control this process

    Article · June 2015
    DOI: 10.7603/s40730-015-0014-0

    Phuc Van Pham
    Ho Chi Minh City University of Science

    Vu Thanh Binh
    Ho Chi Minh City University of Science

    Nhan Lu-Chinh Phan
    Ho Chi Minh City University of Science

    Le Thi Hanh
    Ho Chi Minh City University of Science

    Abstract

    Breast cancer is said to originate from breast cancer stem cells (BCSCs). Previous published studies showed that BCSCs exhibited a high degree of multi-drug resistance. This study aimed to evaluate the spontaneous differentiation of human BCSCs and investigate various in vitro conditions that could be used to control this process. BCSCs were sorted from primary cultures of breast malignant tumors based on expression of CD44 and CD24. The in vitro spontaneous differentiation of BCSCs was evaluated using standard DMEM/F12 medium supplemented with 10% fetal bovine serum (FBS) and 1% antibiotic-antimycotic. There were six different methods tried to control the spontaneous differentiation of BCSCs including culturing in serum-free medium, mammosphere medium, basic fi-broblast growth factor and epidermal growth factor supplemented medium with serum, and culturing under hypoxic conditions. The results showed that BCSCs always spontaneously differentiated in vitro in standard DMEM/F12 plus 10% FBS culture medium. All investigated culture conditions could not completely inhibit the spontaneous differentiation of BCSCs. Serum-free culture medium under hypoxic conditions (mammosphere culture) had the strongest inhibitory effect on this process. These results demonstrated that spontaneous differentiation is a natural process of BCSCs; therefore this process may be somewhat controlled depending on the culture conditions.

  • Breast Cancer Stem Cells & Therapy Resistance

    Breast Cancer Stem Cells & Therapy Resistance

    This volume thoroughly examines breast cancer stem cells (BCSCs), from basic definitions to techniques for identifying, isolating, culturing, and targeting BCSCs for therapy; there is additional focus on pre-clinical and clinical results. The text begins with a discussion of breast cancer, focusing especially on the limitations of current therapies in its treatment. The subsequent chapters introduce and compare stem cells and cancer stem cells, describe properties and isolation techniques of BCSCs, and examine BCSC-targeting approaches. The text concludes with a discussion of controversy surrounding the BCSC hypothesis and of future research directions. Breast Cancer Stem Cells & Therapy Resistance, part of the SpringerBriefs in Stem Cells series, provides a succinct yet comprehensive overview of BCSCs for advanced students, graduate students and researchers as well as those working with breast cancer or stem cells in a clinical setting.

     

    http://www.springer.com/gp/book/9783319220192

     

    Bibliographic Information

    Book Title
    Breast Cancer Stem Cells & Therapy Resistance
    Authors
    • Phuc Van Pham
    Series Title
    SpringerBriefs in Stem Cells
    Copyright
    2015
    Publisher
    Springer International Publishing
    Copyright Holder
    The author(s)
    eBook ISBN
    978-3-319-22020-8
    DOI
    10.1007/978-3-319-22020-8
    Softcover ISBN
    978-3-319-22019-2
    Series ISSN
    2192-8118
    Edition Number
    1
    Number of Pages
    XI, 110
    Number of Illustrations and Tables
    18 in colour
    Topics

  • Stem Cells in Clinical Applications

    Stem Cells in Clinical Applications

    Abstract

    Stem Cells in Clinical Applications brings some of the field’s most renowned scientists and clinicians together with emerging talents and disseminates their cutting-edge clinical research to help shape future therapies. While each book tends to focus on regenerative medicine for a certain organ or system (e.g. Liver, Lung and Heart; Brain and Spinal Cord, etc.) each volume also deals with topics like the safety of stem cell transplantation, evidence for clinical applications including effects and side effects, guidelines for clinical stem cell manipulation and much more. Volumes will also discuss mesenchymal stem cell transplantation in autoimmune disease treatment, stem cell gene therapy in pre-clinical and clinical contexts, clinical use of stem cells in neurological degenerative disease, and best practices for manufacturers in stem cell production. Later volumes will be devoted to Safety, Ethics and Regulations, Stem Cell Banking and Treatment of Cancer and Genetic Disease. This series provides insight not only into novel research in stem cells but also their clinical and real-world contexts. Each book in Stem Cells in Clinical Applications is an invaluable resource for advanced undergraduate students, graduate students, researchers and clinicians in Stem Cells, Tissue Engineering, Biomedical Engineering or Regenerative Medicine.
    http://www.springer.com/series/14002

  • Direct reprogramming of somatic cells: an update

    Direct reprogramming of somatic cells: an update

    Phuc Van Pham

    Abstract

    Direct epigenetic reprogramming is a technique that converts a differentiated adult cell into another differentiated cell—such fibroblasts to cardiomyocytes—without passage through an undifferentiated pluripotent stage. This novel technology is opening doors in biological research and regenerative medicine. Some preliminary studies about direct reprogramming started in the 1980s when differentiated adult cells could be converted into other differentiated cells by overexpressing transcription-factor genes. These studies also showed that differentiated cells have plasticity. Direct reprogramming can be a powerful tool in biological research and regenerative medicine, especially the new frontier of personalized medicine. This review aims to summarize all direct reprogramming studies of somatic cells by master control genes as well as potential applications of these techniques in research and treatment of selected human diseases.

    Keywords

    Direct reprogramming, Trans-differentiation; Induced pluripotent stem cells; Stem cell technology; Gene over-expression

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  • Optimization of culture medium for the isolation and propagation of human breast cancer cells from p

    Biomed Res Ther. 2015; 2(2): 207-219

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

    Binh Thanh Vu, Hanh Thi Le, Nhan Lu-Chinh Phan, Phuc Van Pham

    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.

    Keywords

    Breast cancer; breast cancer stem cell; culture medium; primary cancer cell; tumor biopsy
    Optimization of culture medium for the isolation and propagation of human breast cancer cells from primary tumour biopsies
    Binh Thanh Vu, Hanh Thi Le, Nhan Lu-Chinh Phan, Phuc Van Pham
    Biomed Res Ther. 2015; 2(2): 207-219

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  • New Year Message from Editor

    New Year Message from Editor

    Phuc Van Pham

    Abstract

    The Roman calendar identified January as the month in which looking back and looking forward were both appropriate. Biomedical Research and Therapy (BMRAT) now has one-year history of publication, following a one-year period of preparation, and the first volume has been wrapped up. The vital signs of the journal were positive from the beginning and are becoming stronger all the time.

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  • Production of islet-like insulin-producing cell clusters in vitro from adipose-derived stem cells

    Production of islet-like insulin-producing cell clusters in vitro from adipose-derived stem cells

    Loan Thi-Tung Dang, Anh Nguyen-Tu Bui, Vuong Minh Pham, Ngoc Kim Phan, Phuc Van Pham

    Abstract

    Diabetes mellitus is a high incidence disease that has increased rapidly in recent years. Many new therapies are being studied and developed in order to find an effective treatment. An ideal candidate is stem cell therapy. In this study, we investigated the differentiation of adipose derived stem cells (ADSCs) into pseudo-islets in defined medium in vitro, to produce large quantities of insulin-producing cells (IPCs) for transplantation. ADSCs isolated from adipose tissue were induced to differentiate into islet-like insulin-producing cell clusters in vitro by inducing medium DMEM/F12 containing nicotinamide, N2, B27, bFGF, and insulin-transferrin-selenite (ITS). Differentiated cells were analyzed for properties of IPCs, including storage of Zn2+ by dithizone staining, insulin production by ELISA and immunochemistry, and beta cell-related gene expression by reverse transcriptase PCR. The results showed that after 2 weeks of differentiation, the ADSCs aggregated into cell clusters, and after 4 weeks they formed islets, 50–400 micrometers in diameter. These islet cells exhibited characteristics of pancreatic beta cells as they were positive for dithizone staining, expressed insulin in vitro and C-peptide in the cytoplasm, and expressed pancreatic beta cell-specific genes, including Pdx-1, NeuroD, and Ngn3. These results demonstrate that ADSCs can be used to produce a large number of functional islets for research as well as application.

    Keywords

    Adipose derived stem cells; Beta cells; Diabetes mellitus; In vitro differentiation; Nicotinamid

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  • Targeting specificity of dendritic cells on breast cancer stem cells: in vitro and in vivo evaluatio

    Targeting specificity of dendritic cells on breast cancer stem cells: in vitro and in vivo evaluations

     

     

    Published Date January 2015 Volume 2015:8 Pages 323—334

    DOI http://dx.doi.org/10.2147/OTT.S77554

    Received 15 November 2014, Accepted 3 January 2015, Published 30 January 2015

     

    Sinh Truong Nguyen,1 Huyen Lam Nguyen,1 Viet Quoc Pham,1 Giang Thuy Nguyen,1 Cuong Do-Thanh Tran,1 Ngoc Kim Phan,1,2 Phuc Van Pham1,2

    1Laboratory of Stem Cell Research and Application, 2Faculty of Biology, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam

    Abstract: Breast cancer is a leading cause of death in women, and almost all complications are due to chemotherapy resistance. Drug-resistant cells with stem cell phenotypes are thought to cause failure in breast cancer chemotherapy. Dendritic cell (DC) therapy is a potential approach to eradicate these cells. This study evaluates the specificity of DCs for breast cancer stem cells (BCSCs) in vitro and in vivo. BCSCs were enriched by a verapamil-resistant screening method, and reconfirmed by ALDH expression analysis and mammosphere assay. Mesenchymal stem cells (MSCs) were isolated from allogeneic murine bone marrow. DCs were induced from bone marrow-derived monocytes with 20 ng/mL GC-MSF and 20 ng/mL IL-4. Immature DCs were primed with BCSC- or MSC-derived antigens to make two kinds of mature DCs: BCSC-DCs and MSC-DCs, respectively. In vitro ability of BCSC-DCs and MSC-DCs with cytotoxic T lymphocytes (CTLs) to inhibit BCSCs was tested using the xCELLigence technique. In vivo, BCSC-DCs and MSC-DCs were transfused into the peripheral blood of BCSC tumor-bearing mice. The results show that in vitro BCSC-DCs significantly inhibited BCSC proliferation at a DC:CTL ratio of 1:40, while MSC-DCs nonsignificantly decreased BCSC proliferation. In vivo, tumor sizes decreased from 18.8% to 23% in groups treated with BCSC-DCs; in contrast, tumors increased 14% in the control group (RPMI 1640) and 47% in groups treated with MSC-DCs. The results showed that DC therapy could target and be specific to BCSCs. DCs primed with MSCs could trigger tumor growth. These results also indicate that DCs may be a promising therapy for treating drug-resistant cancer cells as well as cancer stem cells.

    Keywords: dendritic cells, 4T,1 cell line, breast tumor, breast cancer stem cells, verapamil, drug resistance

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  • Mouse model for myocardial injury caused by ischemia

    Mouse model for myocardial injury caused by ischemia

    Truc Le-Buu Pham, Dung Thi-Phuong Nguyen, Oanh Thi-Kieu Nguyen, Tam Thanh Nguyen, Phuc Van Pham

    Abstract

    Mouse model is one of the most useful tools to understand disease’s mechanism as well as evaluate treatment’s efficiency of the disease by novel therapies. To create a mouse model for myocardial injury for cell therapeutic studies, an occluding suture of the left coronary artery in mice was made with sewing thread Prolene 7-0. That left anterior descending artery (LAD) closing caused infarction leading to ischemia and death of cells after that. The animals were then monitored survival ratio, body weight, blood pressure and analyzed Histopathology using Hematoxylin and Eosin (H&E) stain, Trichrome stain, and Immunohistochemistry (IHC) stain to evaluate the injuries of myocardium. The results showed that six weeks after narrowing the left coronary artery, the survival percentage of the experimental group was 77% (survival 17/22), body weight and blood pressure of the experimental group (n=17) tended to decrease comparing to the control group (n=10) or heart function of the experimental group was weakening.  Supporting for that results, Histopathology assessments were also showed that the damages and the death of myocardium in the experiment group. H&E stain gave the presentation that heart septum of the experimental group was thinner than the control group. Collagen formation was also observed in the experimental group by Trichrome stain results. In addition, IHC stain also indicated that the Annexin-V (death cell marker) was expressed much stronger than those of the control group. In conclusion, the mouse model for myocardial injury caused by ischemia has been created successfully by LAD ligation.

    Keywords

    Cardiovascular disease; Coronary arteries; Ischemia; Myocardial infarction; Myocardial injury

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