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The distribution of colony-forming cells among spleen colonies. J Cell Compar Physiol 62:327-36

Journal of Cellular Physiology (Impact Factor: 3.87). 12/1963; 62(3):327-36. DOI: 10.1002/jcp.1030620313
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ABSTRACT Many of the models of hemopoiesis that have been proposed (see, for example, Cronkite et al., '59) are based on the assumption that the continued production of blood cells requires the presence of progenitor cells with the capacity for continued proliferation. From this point of view, hemopoietic tissue may be considered to consist of two compartments; the first, or stem cell compartment, consists of progenitor cells with the capacity to give rise to progeny consisting of both differentiated cells and new stem cells; the second, or differentiated cell compartment, contains cells with limited capacity for cell division, giving rise only to fully differentiated cells. It follows that studies on the processes involved in hemopoiesis require methods for determining the composition of the two compartments. Members of the differentiated cell compartment can frequently be recognized by clear functional markers, for example, the ability to incor- porate radioiron (Alpen and Cranmore, '59). In contrast, recognition and assay of stem cells must involve a procedure in which the descendants of the stem cell are examined. Ideally, such a procedure should test the stem cell not only for its ability to give rise to differentiated descendants (which is the basis for the assay for stem cells described by Gurney and co-workers (Gurney et al., '62)), but should also test for other key properties of stem cells. These include the capacities for self-renewal and extensive proliferation, both of which are required for the maintenance of the stem cell compartment. Recently, a method has been developed which may fulfill these requirements for studies of stem cells. The method depends on the observation that mouse hemopoietic tissue contains a population of cells that have the capacity to give rise to macroscopic colonies in the spleens of irradiated mice (Till and McCulloch, '61; McCulloch and Till, '62). It has been demonstrated by direct cytological means that these colonies originate from single cells (Becker et al., '63), showing that their cells of origin (colony-forming cells) possess sufficient

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    • "Adult stem cells emerge during development and are characterized by loss of pluripotency and a differentiation ability that is tissue restricted. The existence of such cells was first demonstrated in the hematopoietic system with the seminal work of Till and McCulloch showing that cells from the BM can give rise to multilineage descendants while retaining the ability to self-renew (McCulloch and Till, 1960; Siminovitch et al., 1963; Till and McCulloch, 1961). The same tissue was subsequently shown to contain a different population of multipotent cells through the work of Friedenstein and colleagues, who demonstrated that the rodent bone marrow (BM) contains cells that have the ability to form fibroblastoid colonies (CFU-F) when cultured on plastic, make bone, and reconstitute the hematopoietic microenvironment when transplanted subcutaneously (Friedenstein et al., 1968, 1970, 1976, 1982) The ready ability to culture the cells and differentiate them into different mesenchymal lineages in vitro made these cells the subject of intensive investigation for their potential use in regenerative medicine and tissue engineering. "
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    ABSTRACT: Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered first in the bone marrow (BM). They have putative roles in maintaining tissue homeostasis and are increasingly recognized as components of stem cell niches, which are best defined in the blood. The absence of in vivo MSC markers has limited our ability to track their behavior in vivo and draw comparisons with in vitro observations. Here we review the historical background of BM-MSCs, advances made in their prospective isolation, their developmental origin and contribution to maintaining subsets of hematopoietic cells, and how mesenchymal cells contribute to other stem cell niches. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell Stem Cell 03/2015; 16(3):239-253. DOI:10.1016/j.stem.2015.02.019 · 22.15 Impact Factor
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    • "Stem cells are defined for their capability to generate more stem cells – self-renewal– and daughter cells that differentiate [8]. Asymmetric divisions of a stem cell into one stem cell and one differentiated cell will satisfy both these objectives: replenish the stem cell pool and generate the differentiated progenies cycling through the tissue [9] [10]. "
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    ABSTRACT: Cycling tissues such as the intestinal epithelium, germ line, and hair follicles, require a constant flux of differentiated cells. These tissues are maintained by a population of stem cells, which generate differentiated progenies and self-renew. Asymmetric division of each stem cell into one stem cell and one differentiated cell can accomplish both tasks. However, in mammalian cycling tissues, some stem cells divide symmetrically into two differentiated cells and are replaced by a neighbor that divides symmetrically into two stem cells. Besides this heterogeneity in fate (population asymmetry), stem cells also exhibit heterogenous proliferation-rates; in the long run, however, all stem cells proliferate at the same average rate (equipotency). We construct and simulate a mathematical model based on these experimental observations. We show that the complex steady-state dynamics of population-asymmetric stem cells reduces the rate of replicative aging of the tissue - potentially lowering the incidence of somatic mutations and genetics diseases such as cancer. Essentially, slow-dividing stem cells proliferate and purge the population of the fast-dividing - older - cells which had undertaken the majority of the tissue-generation burden. As the number of slow-dividing cells grows, their cycling-rate increases, eventually turning them into fast-dividers, which are themselves replaced by newly emerging slow-dividers. Going beyond current experiments, we propose a mechanism for equipotency that can potentially halve the rate of replicative aging. Our results highlight the importance of a population-level understanding of stem cells, and may explain the prevalence of population asymmetry in a wide variety of cycling tissues.
    Journal of Theoretical Biology 04/2013; 331. DOI:10.1016/j.jtbi.2013.04.018 · 2.30 Impact Factor
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    • "Mesenchymal stem (stromal) cells (MSC)—are one of the most important instruments of modern regenerative medicine. Though MSC have been known since 1960–1970s (Becker et al. 1963, Siminovitch et al. 1963, Friedenstein et al. 1974, 1976, Pittenger et al. 1999), practical interest in them was only seen at the beginning of the XXI century. However there was dispute over nomenclature and the standardization criteria of belonging to this group of cells. "
    Biomaterials for Stem Cell Therapy: State of Art and Vision for the Future, Edited by Loredana De Bartolo, Augustinus Bader, 01/2013: chapter 8: pages 212-227; CRC Press., ISBN: 9781466576391
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