The Hematopoietic Stem Cell in its Place

Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Nature Immunology (Impact Factor: 20). 05/2006; 7(4):333-7. DOI: 10.1038/ni1331
Source: PubMed


A signature characteristic of stem cells is their ability to self-renew, affording a theoretically limitless ability to produce daughter cells and their descendents. This near-timeless dimension of stem cell function is not free of the constraints of place. The idea that highly specialized 'microenvironmental' cues participate in the regulation of stem cells has evidence in classic embryology and more recently in adult stem cells through the use of model organisms. There is now ample evidence that an anatomically defined, specifically constituted place represents the niche for hematopoietic and other tissue-specific stem cells. This review provides a conceptual framework and detailed account of the hematopoietic stem cell niche as defined at present. The components are assembling into a more complex view of the niche and may now be amenable to examination as a system and possibly to alteration to affect outcomes in immune regeneration.


Available from: Gregor B. Adams, Jun 08, 2015
    • "These precursors, originate mature cells through progressive cell differentiation and, in some of the phases, intensive proliferation [Huang et al., 2007]. Compared to mature lymphocytes, HPC have different signal requirements for survival or apoptosis induction and undergo complex processes [Adams and Scadden, 2006]. The development of B and T cells bearing antigen-specific receptors requires gene rearrangements with consequent generation of double strand breaks (and DNA repair) followed by intense cell proliferation, rendering lymphocytes susceptible to oncogenic transformation. "
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    ABSTRACT: Studies describing the influence of radiofrequency electromagnetic fields on bone marrow cells (BMC) often lack functional data. We examined the effects of in vivo exposure to a Global System for Mobile Communications (GSM) modulated 900 MHz RF fields on BMC using two transplantation models. X-irradiated syngeneic mice were injected with BMC from either RF-field-exposed, sham-exposed or cage control mice. Twelve weeks after transplantation, no differences in thymocyte number, frequency of subpopulations and cell proliferation were found in mice receiving BMC from either group. Also, in the spleen cell number, percentages of B/T cells, B/T-cell proliferation, and interferon γ (IFN-γ) production were similar in all groups. In parallel, a mixture of BMC from congenic sham- and RF-exposed mice were co-transplanted into lymphopenic Rag2 deficient mice. BMC from RF-exposed and sham-exposed mice displayed no advantage or disadvantage when competing for the replenishment of lymphatic organs with mature lymphocytes in Rag2 deficient mice. This model revealed that BMC from sham-exposed and RF-exposed mice were less efficient than BMC from cage control mice in repopulating the thymus, an effect likely due to restraint stress. In conclusion, our results showed no effects of in vivo exposure to GSM-modulated RF-fields on the ability of bone marrow (BM) precursors to long-term reconstitute peripheral T and B cell compartments. Bioelectromagnetics © 2014 Wiley Periodicals, Inc.
    Bioelectromagnetics 12/2014; 35(8). DOI:10.1002/bem.21880 · 1.71 Impact Factor
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    • "Th e interaction between stem cells and their niche involves the interplay of many factors, including extracellular matrix (ECM) molecules, cell-cell contacts, and cytokines. Th is interplay critically balances cell cycling and quiescence, leading to proliferation or apoptosis, and selfrenewal or diff erentiation, respectively (Adams and Scadden 2006, Wilson and Trumpp 2006, Yin and Li 2006). Several stem cell niches have been described for diverse adult stem cells, which contribute to tissue homeostasis of an organism and are located inside the bone marrow, retina, cornea, gastrointestinal tract, pancreas, etc. "
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    ABSTRACT: Background: Tumor initiation, growth and relapse after therapy are thought to be driven by a population of cells with stem cell characteristics, named cancer stem cells (CSC). The regulation of their radiation resistance and their maintenance is poorly understood. CSC are believed to reside preferentially in special microenvironmental niches located within tumor tissues. The features of these niches are of crucial importance for CSC self-renewal, metastatic potential and therapy resistance. One of the characteristics of solid tumors is occurrence of less oxygenated (hypoxic regions), which are believed to serve as so-called hypoxic niches for CSC. Purpose: The purpose of this review was the critical discussion of the supportive role of hypoxia and hypoxia-related pathways during cancer progression and radiotherapy resistance and the relevance for therapeutic implications in the clinic. Conclusion: It is generally known since decades that hypoxia inside solid tumors impedes chemo- and radiotherapy. However, there is limited evidence to date that targeting hypoxic regions during conventional therapy is effective. Nonetheless improved hypoxia-imaging technologies and image guided individualized hypoxia targeted therapy in conjunction with the development of novel molecular targets may be able to challenge the protective effect on the tumor provided by hypoxia.
    International Journal of Radiation Biology 05/2014; 90(8):1-80. DOI:10.3109/09553002.2014.916841 · 1.69 Impact Factor
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    • "cells, fibroblasts and adipocytes, which create a supportive environment for stem cells [3]. Interactions between these components determine the proliferation, spread, and survival of plasma cells, as well as their acquisition of drug resistance and the development of relapse [4] [5] [6]. "
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    ABSTRACT: In patients with multiple myeloma (MM), the bone marrow (BM) contains hematopoietic stem cells (HSCs) and non-hematopoietic cells. HSCs are able to give rise to all types of mature blood cells, while the non hematopoietic component includes mesenchymal stem cells (MSCs), fibroblasts, osteoblasts, osteoclasts, chondroclasts, endothelial cells, endothelial progenitor cells (EPCs), B and T lymphocytes, NK cells, erythrocytes, megakaryocytes, platelets, macrophages and mast cells. All of these cells form specialized "niches" in the BM microenvironment which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche"). The "vascular niche" is rich in blood vessels where endothelial cells and mural cells (pericytes and smooth muscle cells) create a microenvironment that affects the behavior of several stem and progenitor cells. The vessel wall serves as an independent niche for the recruitment of endothelial progenitor cells, MSCs and HSCs. The activation by angiogenic factors and inflammatory cytokines switch the "vascular niche" to promote MM tumor growth and spread. This review will focus on the mechanisms involved in the generation of signals released by endothelial cells in the "vascular niche" that promote tumor growth and spread in MM. © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 05/2014; 133 Suppl 2(2):S102-6. DOI:10.1016/S0049-3848(14)50017-5 · 2.45 Impact Factor
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