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James L. Sherley - One of the best experts on this subject based on the ideXlab platform.

  • Clonal expansion of adult rat hepatic stem Cell lines by suppression of asymmetric Cell Kinetics (SACK).
    Biotechnology and bioengineering, 2003
    Co-Authors: Hsuan-shu Lee, Gracy G. Crane, Joshua R. Merok, James R. Tunstead, Nicole L. Hatch, Krishnanchali Panchalingam, Mark J. Powers, Linda G. Griffith, James L. Sherley
    Abstract:

    Adult stem Cells have potential use for several biomedical applications, including Cell replacement therapy, gene therapy, and tissue engineering. However, such applications have been limited due to difficulties encountered in expanding functional adult stem Cells. We have developed a new approach to the problem of adult stem Cell expansion based on the suppression of asymmetric Cell Kinetics (SACK). We postulated that asymmetric Cell Kinetics, required for adult stem Cell function, were a major barrier to their expansion in culture. As such, conversion of adult stem Cells from asymmetric Cell Kinetics to symmetric Cell Kinetics would promote their exponential expansion and longterm propagation in culture. The purine nucleoside xanthosine (Xs), which promotes guanine ribonucleotide biosynthesis, can be used to reversibly convert Cells from asymmetric Cell Kinetics to symmetric Cell Kinetics. We used Xs supplementation to derive clonal epithelial Cell lines from adult rat liver that have properties of adult hepatic stem Cells. The properties of two Xs-derived Cell lines, Lig-8 and Lig-13, are described in detail and compared to properties of adult rat hepatic Cell lines derived without Xs supplementation. The Xs-derived Cell lines exhibit Xs-dependent asymmetric Cell Kinetics and Xs-dependent expression of mature hepatic differentiation markers. Interestingly, Lig-8 Cells produce progeny with properties consistent with hepatocyte differentiation, while Lig-13 progeny Cells have properties consistent with bile duct epithelium differentiation. A stable adult cholangiocyte stem Cell line has not been previously described. Consistent with the principles of their derivation, the SACK-derived hepatic Cell lines exhibit neither senescence nor tumorigenic properties, and their differentiation properties are stable after longterm culture. These characteristics of SACK-derived stem Cell lines underscore asymmetric Cell Kinetics as an essential adult stem Cell property with potential to be the basis for a general approach to expansion and propagation of diverse adult stem Cells.

  • Asymmetric Cell Kinetics genes: the key to expansion of adult stem Cells in culture.
    TheScientificWorldJournal, 2002
    Co-Authors: James L. Sherley
    Abstract:

    A singular challenge in stem Cell research today is the expansion and propagation of functional adult stem Cells. Unlike embryonic stem Cells, which are immortal in culture, adult stem Cells are notorious for the difficulty encountered when attempts are made to expand them in culture. One overlooked reason for this difficulty may be the inherent asymmetric Cell Kinetics of stem Cells in postnatal somatic tissues. Senescence is the expected fate of a culture whose growth depends on adult stem Cells that divide with asymmetric Cell Kinetics. Therefore, the bioengineering of strategies to expand adult stem Cells in culture requires knowledge of Cellular mechanisms that control asymmetric Cell Kinetics. The properties of several genes recently implicated to function in a Cellular pathway(s) that regulates asymmetric Cell Kinetics are discussed. Understanding the function of these genes in asymmetric Cell Kinetics mechanisms may be the key that unlocks the adult stem Cell expansion problem.

  • Cellular Senescence: Ex Vivo p53-Dependent Asymmetric Cell Kinetics.
    Journal of biomedicine & biotechnology, 2001
    Co-Authors: Lakshmi Rambhatla, Shirley A. Bohn, Patrizia B. Stadler, Jonathan T. Boyd, Ronald A. Coss, James L. Sherley
    Abstract:

    Although senescence is a defining property of euploid mammalian Cells, its physiologic basis remains obscure. Previously, Cell Kinetics properties of normal tissue Cells have not been considered in models for senescence. We now provide evidence that senescence is in fact the natural consequence of normal in vivo somatic stem Cell Kinetics extended in culture. This concept of senescence is based on our discovery that Cells engineered to conditionally express the well-recognized tumor suppressor protein and senescence factor, p53, exhibit asymmetric Cell Kinetics. In vivo, asymmetric Cell Kinetics are essential for maintenance of somatic stem Cells; ex vivo, the same Cell Kinetics yield senescence as a simple kinetic endpoint. This new “asymmetric Cell Kinetics model” for senescence suggests novel strategies for the isolation and propagation of somatic tissue stem Cells in culture.

Jens Overgaard - One of the best experts on this subject based on the ideXlab platform.

James J. Going - One of the best experts on this subject based on the ideXlab platform.

  • Cell Kinetics in vivo of human breast cancer
    The British journal of surgery, 1996
    Co-Authors: P. D. Stanton, Timothy G. Cooke, G. Forster, D. Smith, James J. Going
    Abstract:

    Rates of Cell proliferation within tumours may provide prognostic information and help in the rational administration of chemotherapy and radiotherapy. In vivo labelling with 5-bromo-2'-deoxyuridine (BrdU) was used in 89 women with breast cancer to determine the labelling index for BrdU (BLI), the length of S phase (T s ) and the potential doubling time of the tumour (T pot ). Kinetic data were obtained in 84 patients. The median BLI was 3.2 per cent, T s 12 h, and T pot 12.5 days. There was no systematic difference in the labelling index determined by flow cytometry and by manual counting on sections. Labelling indices were significantly higher in aneuploid tumours, and in tumours not expressing oestrogen receptors, but were not correlated with tumour size, nodal status, or expression of c-erbB2. In vivo measurement of tumour Cell Kinetics can be made rapidly and reliably in the majority of human breast cancers, and may have a role to play in planning therapy.

Cristina Ghirelli - One of the best experts on this subject based on the ideXlab platform.

  • The in vivo Cell Kinetics in breast carcinogenesis
    Breast Cancer Research, 2001
    Co-Authors: Niki J Agnantis, Sevasti Kamina, P. Zagorianakou, A Katsaraki, Roberto Agresti, Asymo Demou, Elda Tagliabue, Panagiotis Kanavaros, Cristina Ghirelli
    Abstract:

    Background Disruption of the balance between apoptosis and proliferation is considered to be an important factor in the development and progression of tumours. In the present study we determined the in vivo Cell Kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis.

L Nerstrøm Salling - One of the best experts on this subject based on the ideXlab platform.