Siminovitch L, McCulloch EA, Till JEThe distribution of colony-forming cells among spleen colonies. J Cell Physiol 62:327-336

Journal of Cellular Physiology (Impact Factor: 3.84). 12/1963; 62(3):327-36. DOI: 10.1002/jcp.1030620313
Source: PubMed


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.
    Full-text · Article · Mar 2015 · Cell Stem Cell
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    • "Early evidence of differences between the biological properties of primitive hematopoietic cells from fetal and adult tissues were revealed from investigations of mouse hematopoietic cells that form macroscopically visible clones of differentiating blood cells in the spleen of irradiated mice injected 9–14 days previously.13 These so-called colony-forming units-spleen (CFU-S) were initially thought to detect a fraction of HSCs that colonize the spleen because they could generate all myeloid cell types (erythroid, megakaroyopoietic and granulopoietic) as well as progeny CFU-S with similar potentialities demonstrable in secondary transplants.14, 15 However, it is now known that most CFU-S do not overlap with HSCs that possess lifelong repopulating ability. "
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    ABSTRACT: Hematopoietic stem cells (HSCs) comprise a rare population of cells that can regenerate and maintain lifelong blood cell production. This functionality is achieved through their ability to undergo many divisions without activating a poised, but latent, capacity for differentiation into multiple blood cell types. Throughout life, HSCs undergo sequential changes in several key properties. These affect mechanisms that regulate the self-renewal, turnover and differentiation of HSCs as well as the properties of the committed progenitors and terminally differentiated cells derived from them. Recent findings point to the Lin28b-let-7 pathway as a master regulator of many of these changes with important implications for the clinical use of HSCs for marrow rescue and gene therapy, as well as furthering our understanding of the different pathogenesis of childhood and adult-onset leukemia.
    Full-text · Article · Nov 2013
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    • "Since 1963, when the isolation and self-renewing properties of mouse bone marrow cells were first reported [78, 79], until now most of the research efforts have been focused on the identification of molecular markers [4, 80, 81]. This has allowed the isolation of different types of tissue-specific stem or progenitor cells [82–85] and has also assisted to define the differentiation of stem or progenitor cells into a particular cell type [86, 87]. "
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    ABSTRACT: Cell-based regenerative therapies, based on in vitro propagation of stem cells, offer tremendous hope to many individuals suffering from degenerative diseases that were previously deemed untreatable. Due to the self-renewal capacity, multilineage potential, and immunosuppressive property, mesenchymal stem cells (MSCs) are considered as an attractive source of stem cells for regenerative therapies. However, poor growth kinetics, early senescence, and genetic instability during in vitro expansion and poor engraftment after transplantation are considered to be among the major disadvantages of MSC-based regenerative therapies. A number of complex inter- and intracellular interactive signaling systems control growth, multiplication, and differentiation of MSCs in their niche. Common laboratory conditions for stem cell culture involve ambient O2 concentration (20%) in contrast to their niche where they usually reside in 2-9% O2. Notably, O2 plays an important role in maintaining stem cell fate in terms of proliferation and differentiation, by regulating hypoxia-inducible factor-1 (HIF-1) mediated expression of different genes. This paper aims to describe and compare the role of normoxia (20% O2) and hypoxia (2-9% O2) on the biology of MSCs. Finally it is concluded that a hypoxic environment can greatly improve growth kinetics, genetic stability, and expression of chemokine receptors during in vitro expansion and eventually can increase efficiency of MSC-based regenerative therapies.
    Full-text · Article · Aug 2013 · The Scientific World Journal
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