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There are many definitions of the term “ageing” and perhaps even more theories that seek to explain its causes (Balcombe and Sinclair 2001). From a physiological standpoint, ageing beyond reproductive maturity is often viewed as a progression of multisystem deficits in tissue function. In adult mammals, tissue homeostasis is maintained by stem cell populations that reside in, or migrate between, a variety of adult tissues. These stem cells ensure proper tissue function by generating new cells to replace those lost or damaged over time. Despite the presence of adult stem cells in muscle, nervous, gastrointestinal, hematopoietic, and other tissues, each of these systems exhibit functional decline with age (Edwards et al. 2002, Campisi 2003, Kondo et al. 2003, Penninx et al. 2003, Pinto et al. 2003, Linton and Dorshkind 2004, Balducci and Ershler 2005, Fulle et al. 2005, Kamminga 2005, Bauer et al. 2006, Keller 2006, Theise 2006). It is compelling to consider that functional changes in the stem cell compartment of adult tissues precedes and perhaps contributes to the manifestation of ageing phenotypes. In this chapter we will review literature describing the effects of ageing on the well-characterized stem cells of the hematopoietic system. In this system, ageing is accompanied by immune compromise, anemia, and a dramatic increase in the incidence of malignancy (Edwards et al. 2002, Campisi 2003, Penninx et al. 2003, Pinto et al. 2003, Linton and Dorshkind 2004, Balducci and Ershler 2005). Several studies support the hypothesis that these ageing phenotypes stem from functional changes in hematopoietic stem cells (HSCs).

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References

  • Abkowitz JL, Robinson AE, Kale S, Long MW, JC (2003) Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood 102:1249–53.

    Google Scholar 

  • Abramovich C, Humphries R (2005) Hox regulation of normal and leukemic hematopoietic stem cells. Curr Opin Hematol 12:210–16.

    Article  PubMed  CAS  Google Scholar 

  • Abramovich C, Pineault N, Ohta H, Humphries RK (2005) Hox genes: from leukemia to hematopoietic stem cell expansion. Ann NY Acad Sci 1044:109–16.

    Article  PubMed  CAS  Google Scholar 

  • Adams GB et al. (2006) Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439:599–603.

    Article  PubMed  CAS  Google Scholar 

  • Alvarez-Dolado M et al. (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968–73.

    Article  PubMed  CAS  Google Scholar 

  • Antonchuk J, Sauvageau G, Humphries RK (2002) HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 109:39–45.

    Article  PubMed  CAS  Google Scholar 

  • Arai F et al. (2004) Tie2/Angiopoietin-1 Signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118:149–61.

    Article  PubMed  CAS  Google Scholar 

  • Askenasy N, Stein J, Yaniv I, Farkas D (2003) The topologic and chronologic patterns of hematopoietic cell seeding in host femoral bone marrow after transplantation. Bio Blood Marrow Tr 9:496–504.

    Article  Google Scholar 

  • Avecilla ST et al. (2004) Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Med 10:64–71.

    Article  PubMed  CAS  Google Scholar 

  • Avigdor A et al. (2004) CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood 103:2981–89.

    Article  PubMed  CAS  Google Scholar 

  • Balcombe NR, Sinclair A (2001) Ageing: definitions, mechanisms and the magnitude of the problem. Best Pract Res Cl Ga 15:835–49.

    Article  CAS  Google Scholar 

  • Balducci L, Ershler WB (2005) Cancer and ageing: a nexus at several levels. Nature 5:655–62.

    CAS  Google Scholar 

  • Balsam L, Wagers A, Christensen J, Kofidis T, Weissman I, Robbins R (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428:668–73.

    Article  PubMed  CAS  Google Scholar 

  • Bauer H, Tempfer H, Bernroider G, Bauer H (2006) Neuronal stem cells in adults. Exp Gerontol 4:111–16.

    Article  CAS  Google Scholar 

  • Becker AJ, McCulloch EA, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–4.

    Article  PubMed  CAS  Google Scholar 

  • Bell DR, Van Zant G (2004) Stem cells, ageing, and cancer: inevitabilities and outcomes. Oncogene 23:7290–96.

    Article  PubMed  CAS  Google Scholar 

  • Boyer LA et al. (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441:349–53.

    Article  PubMed  CAS  Google Scholar 

  • Buckner CD (1999) Autologous bone marrow transplants to hematopoietic stem cell support with peripheral blood stem cells: a historical perspective. J Hematother 8:233–36.

    Article  PubMed  CAS  Google Scholar 

  • Calabrese C et al. (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11:69–82.

    Article  PubMed  CAS  Google Scholar 

  • Calvi LM et al. (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–46.

    Article  PubMed  CAS  Google Scholar 

  • Campisi J (2003) Cancer and ageing: rival demons? Nature 3:339–49.

    CAS  Google Scholar 

  • Campisi J (2005) Senescent cells, tumor suppression, and organismal ageing: good citizens, bad neighbors. Cell 120:513–22.

    Article  PubMed  CAS  Google Scholar 

  • Cancelas JA, Jansen M, Williams DA (2006) The role of chemokine activation of Rac GTPases in hematopoietic stem cell marrow homing, retention, and peripheral mobilization. Exp Hematol 34:976–85.

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Astle CM, Harrison DE (1999) Development and ageing of primitive hematopoietic stem cells in BALB/cBy mice. Exp Hematol 27:928–35.

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Astle CM, Harrison DE (2000) Genetic regulation of primitive hematopoietic stem cell senescence. Exp Hematol 28:442–50.

    Article  PubMed  CAS  Google Scholar 

  • Cheng T, Rodrigues N, Dombkowski DM, Stier S, Scadden DT (2000a) Stem cell repopulation efficiency but not pool size is governed by p27(kip1). Nature Med 6:1235–40.

    Article  PubMed  CAS  Google Scholar 

  • Cheng T et al. (2000b) Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287:1804–08.

    Article  PubMed  CAS  Google Scholar 

  • Christensen JL, Wright DE, Wagers AJ, Weissman IL (2004) Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol 2:0368–77.

    Article  Google Scholar 

  • Chute JP (2006) Stem cell homing. Curr Opin Hematol 13:399–406.

    Article  PubMed  Google Scholar 

  • Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127:469–80.

    Article  PubMed  CAS  Google Scholar 

  • Cui J et al. (1999) Bone marrow cell trafficking following intravenous administration. Br J Haematol 107:895–902.

    Article  PubMed  CAS  Google Scholar 

  • Dar A, Kollet O, Lapidot T (2006) Mutual, reciprocal SDF-1/CXCR4 interactions between hematopoietic and bone marrow stromal cells regulate human stem cell migration and development in NOD/SCID chimeric mice. Exp Hematol 34:967–75.

    Article  PubMed  CAS  Google Scholar 

  • Dawn B, Bolli R (2005) Adult bone marrow-derived cells: Regenerative potential, plasticity, and tissue commitment. Basic Res Cardiol 100:494–503.

    Article  PubMed  CAS  Google Scholar 

  • de Haan G, Nijhof W, Van Zant G (1997) Mouse strain-dependent changes in frequency and proliferation of hemaotpoietic stem cells during ageing: Correlation between life span and cycling activity. Blood 89.

    Google Scholar 

  • de Haan G, Van Zant G (1997) Intrinsic and extrinsic control of hemopoietic stem cell numbers: Mapping of a stem cell gene. J Exp Med 186:529–36.

    Article  PubMed  Google Scholar 

  • de Haan G, Van Zant G (1999) Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span. FASEB J 13:707–13.

    PubMed  Google Scholar 

  • de Haan G, Van Zant, Gary (1999) Dynamic changes in mouse hematopoietic stem cell numbers during ageing. Blood 93:3294–3301.

    PubMed  Google Scholar 

  • Dubrulle J, McGrew MJ, Pourquie O (2001) FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell 106:219–32.

    Article  PubMed  CAS  Google Scholar 

  • Dumble M et al. (2007) The impact of altered p53 dosage on hematopoietic stem cell dynamics during ageing. Blood 109:1736–42.

    Article  PubMed  CAS  Google Scholar 

  • Duncan AW et al. (2005) Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 6:314–22.

    Article  PubMed  CAS  Google Scholar 

  • Edwards B et al. (2002) Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and ageing on U.S. cancer burden. Cancer 94:2766–92.

    Article  PubMed  Google Scholar 

  • Eglitis M, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc. Natl. Acad. Sci. USA 94:4080–05.

    Article  PubMed  CAS  Google Scholar 

  • Ezoe S, Matsumura I, Sato Y, Tanaka H, Kanakura Y (2004) Cell cycle regulation in hematopoietic stem/progenitor cells. Cell Cycle 3:314–18.

    PubMed  CAS  Google Scholar 

  • Fernandis AZ, Prasad A, Band H, Klosel R, Ganju RK (2004) Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells. Oncogene 23:157–67.

    Article  PubMed  CAS  Google Scholar 

  • Ferrari G et al. (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279:1528–30.

    Article  PubMed  CAS  Google Scholar 

  • Frenette PS, Subbarao S, Mazo I, von Andrian UH, Wagner DD (1998) Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow. Proc Natl Acad Sci USA 95:14423–28.

    Article  PubMed  CAS  Google Scholar 

  • Fu S, Liesveld J (2000) Mobilization of hematopoietic stem cells. Blood Rev 14:205–18.

    Article  PubMed  CAS  Google Scholar 

  • Fulle S et al. (2005) Age-dependent imbalance of the antioxidative system in human satellite cells. Exp Gerontol 40:189–97.

    Article  PubMed  CAS  Google Scholar 

  • Geiger H, True JM, de Haan G, Van Zant G (2001) Age- and stage-specific regulation patterns in the hematopoietic stem cell hierarchy. Blood 98:2966–72.

    Article  PubMed  CAS  Google Scholar 

  • Goodman JW, Hodgson GS (1962) Evidence for stem cells in the peripheral blood of mice. Blood 19:702–14.

    PubMed  CAS  Google Scholar 

  • Harman D (1956) Ageing: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300.

    PubMed  CAS  Google Scholar 

  • Harrison DE (1979) Mouse erythropoietic stem cell lines function normally 100 months: loss related to number of transplantations. Mech Ageing Dev 9:427–33.

    Article  PubMed  CAS  Google Scholar 

  • Harrison DE, Astle CM (1982) Loss of stem cell repopulating ability upon transplantation; Effects of donor age, cell number, and transplantation procedure. J Exp Med 156:1767–79.

    Article  PubMed  CAS  Google Scholar 

  • Harrison DE, Astle CM, Stone M (1989) Numbers and functions of transplantable primitive immunohematopoietic stem cells. Effects of age. J Immunol 142:3833.

    PubMed  CAS  Google Scholar 

  • Hock H et al. (2004) Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells. Nature 431:1002–07.

    Article  PubMed  CAS  Google Scholar 

  • Houghton J et al. (2004) Gastric cancer originating from bone marrow-derived cells. Science 306:1568–71.

    Article  PubMed  CAS  Google Scholar 

  • Ito K et al. (2006) Reactive oxygen species act through p38 MAPK to limit the life span of hematopoietic stem cells. Nature Med 12:446–51.

    Article  PubMed  CAS  Google Scholar 

  • Janzen V et al. (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443:421–26.

    PubMed  CAS  Google Scholar 

  • John A, Tuszynski G (2001) The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol Oncol Res 7:14–23.

    Article  PubMed  CAS  Google Scholar 

  • Juttner CA, To LB, Haylock DN, Brandford A, Kimber RJ (1985) Circulating autologous stem cells collected in very early remission from acute non-lymphoblastic leukaemia produce prompt but incomplete haemopoietic reconstitution after high dose melphalan or supralethal chemoradiotherapy. Br J Haematol 61:739–45.

    Article  PubMed  CAS  Google Scholar 

  • Kamminga LM. vOR, Ausema A, Noach EJ, Weersing E, Dontje B., Vellenga E., de Haan, Gerald (2005) Impaired hematopoietic stem cell functioning after serial transplantation and during normal ageing. Stem Cells 23:82–92.

    Google Scholar 

  • Kamminga LM et al. (2006) The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 2006:5.

    Google Scholar 

  • Kamminga LM, de Haan G (2006) Cellular memory and hematopoietic stem cell ageing. Stem Cells 24:1143–9.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan RN, Psaila B, Lyden D (2006) Bone marrow cells in the ‘pre-metastatic niche’: within bone and beyond. Cancer Metastasis Rev 25:521–29.

    Article  PubMed  Google Scholar 

  • Keller J (2006) Age-related neuropathology, cognitive decline, and Alzheimer’s disease. Ageing Res Rev 5:1–13.

    Article  PubMed  CAS  Google Scholar 

  • Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121:1109–21.

    Article  PubMed  CAS  Google Scholar 

  • Kim CH, Broxmeyer HE (1998) In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: stromal cell-derived factor-1, steel factor, and the bone marrow environment. Blood 91:100–10.

    PubMed  CAS  Google Scholar 

  • Kim M, Moon HB, Spangrude GJ (2003) Major age-related changes of mouse hematopoietic stem/progenitor cells. Ann NY Acad Sci 996:195–208.

    Article  PubMed  Google Scholar 

  • Kimura T et al. (2004) The sphingosine 1-phosphate receptor agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34+ progenitor cells. Blood 103:4478–86.

    Article  PubMed  CAS  Google Scholar 

  • Klassen LW (1972) Experimental medullary aplasia. J Lab Clin Med 80:8–17.

    PubMed  CAS  Google Scholar 

  • Kojika S, Griffin JD (2001) Notch receptors and hematopoiesis. Exp Hematol 29:1041–52.

    Article  PubMed  CAS  Google Scholar 

  • Kollet O et al. (2003) HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver. J Clin Invest 112:160–09.

    PubMed  CAS  Google Scholar 

  • Kondo M et al. (2003) Biology of hematopoietic stem cells and progenitors: Implications for clinical application. Ann Rev Immunol 21:759–806.

    Article  CAS  Google Scholar 

  • Krause DJ, Lazarides K, von Andrian UH, Van Etten RA (2006) Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nature Med 12:1175–80.

    Article  PubMed  CAS  Google Scholar 

  • Krishnamurthy J et al. (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453–57.

    Article  PubMed  CAS  Google Scholar 

  • Krishnamurthy J et al. (2004) Ink4a/Arf expression is a biomarker of ageing. J Clin Invest 114:12997–11307.

    Google Scholar 

  • Krosl J, Austin P, Beslu N, Kroon E, Humphries RK, Sauvageau G (2003) In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein. Nature Med 9:1428–32.

    Article  PubMed  CAS  Google Scholar 

  • Kucia M et al. (2006) A population of very small embryonic-like (VSEL) CXCR4(+) SSEA-1(+) Oct-4+ stem cells identified in adult bone marrow. Leukemia 20:857–69.

    Article  PubMed  CAS  Google Scholar 

  • Labrie JE, Sah AP, Allman DM, Cancro MP, Gerstein RM (2004) Bone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged mice. J Exp Med 200:411–23.

    Article  PubMed  CAS  Google Scholar 

  • Lanzkron SM, Collector MI, Sharkis SJ (1999) Homing of long-term and short-term engrafting cells in vivo. Ann NY Acad Sci 872:48–54.

    Article  PubMed  CAS  Google Scholar 

  • Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Biol Blood Marrow Tr 106:1901–10.

    CAS  Google Scholar 

  • Lapidot T, Petit I (2002) Current understanding of stem cell mobilization: The roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 30:973–81.

    Article  PubMed  CAS  Google Scholar 

  • Lawrence HJ, Sauvageau G, Humphries RK, Largman C (1996) The role of HOX homeobox genes in normal and leukemic hematopoiesis. Stem Cells 14:281–91.

    Article  PubMed  CAS  Google Scholar 

  • Lessard J, Baban S, Sauvageau G (1998) Stage-specific expression of polycomb group genes in human bone marrow cells. Blood 91:1216–24.

    PubMed  CAS  Google Scholar 

  • Levesque JP, Hendy J, Takamatsu Y, Williams B, Winker IG, Simmons PJ (2002) Mobilization by either cyclophosphamide or granulocyte colony-stimulating factor transforms the bone marrow into a highly proteolytic environment. Exp Hematol 30:440–49.

    Article  PubMed  CAS  Google Scholar 

  • Lewis EB (1978) A gene complex controlling segmentation in Drosophila. Nature 276:565–70.

    Article  PubMed  CAS  Google Scholar 

  • Li F, Tiede B, Massague J, Kang Y (2007) Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res 17:3–14.

    Article  PubMed  CAS  Google Scholar 

  • Li L, Neaves WB (2006) Normal stem cells and cancer stem cells: the niche matters. Cancer Res 66:4553–57.

    Article  PubMed  CAS  Google Scholar 

  • Li W, Johnson SA, Shelley WC, Yoder MC (2004) Hematopoietic stem cell repopulating ability can be maintained in vitro by some primary endothelial cells. Exp Hematol 32:1226–37.

    Article  PubMed  CAS  Google Scholar 

  • Li Z, Li L (2006) Understanding hematopoietic stem-cell microenvironments. Trends Biochem Sci 31:589–95.

    Article  PubMed  CAS  Google Scholar 

  • Liang Y, Van Zant G, Szilvassy SJ (2005) Effects of ageing on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 106:1479–87.

    Article  PubMed  CAS  Google Scholar 

  • Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nature Immunol 5:133–39.

    Article  CAS  Google Scholar 

  • Marley SB, Lewis JL, Davidson RJ, Roberts IA, Dokal I, Goldman JM (1999) Evidence for a continuous decline in haemopoietic cell function from birth: an application to evaluating bone marrow failure in children. Br J Haematol 106:162–66.

    Article  PubMed  CAS  Google Scholar 

  • Mazo I, J-C G-R, Frenette PS, Hynes RO, Wagner DD, von Andrian UH (1998) Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1. J Exp Med 188:465–74.

    Article  PubMed  CAS  Google Scholar 

  • McCredie KB, Hersh EM, Freireich EJ (1971) Cells capable of colony formation in the peripheral blood of man. Science 171:293–94.

    Article  PubMed  CAS  Google Scholar 

  • McCulloch EA, Till JE (1960) The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiat Res 13:115–125.

    Article  PubMed  CAS  Google Scholar 

  • Miller JP, Allman D (2003) The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors. J Immunol 171:2326–30.

    PubMed  CAS  Google Scholar 

  • Min H, Montecino-Rodriquez E, Dorshkind K (2005) Effects of ageing on early B- and T- cell development. Immunol Rev 205:7–17.

    Article  PubMed  CAS  Google Scholar 

  • Min H, Montecino-Rodriquez E, Dorshkind K (2006) Effects of ageing on the common lymphoid progenitor to pro-B cell transition. J Immunol 176:1007–12.

    PubMed  CAS  Google Scholar 

  • Mintz B, Silvers WK (1967) “Intrinsic” immunological tolerance in allophenic mice. Science 158:1484–86.

    Article  PubMed  CAS  Google Scholar 

  • Miyake N, Brun AC, Magnusson M, Miyake K, Scadden DT, Karlsson S (2006) HOXB4-induced self-renewal of hematopoietic stem cells is significantly enhanced by p21 deficiency. Stem Cells 24:653–61.

    Article  PubMed  CAS  Google Scholar 

  • Molofsky AV et al. (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448–52.

    Article  PubMed  CAS  Google Scholar 

  • Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL (1996) The ageing of hematopoietic stem cells. Nature Med 2:1011–16.

    Article  PubMed  CAS  Google Scholar 

  • Murry C et al. (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428:664–68.

    Article  PubMed  CAS  Google Scholar 

  • Na Nakorn T, Traver D, Weissman IL, Akashi K (2002) Myeloerythroid-restricted progenitors are sufficient to confer radioprotection and provide the majority of day 8 CFU-S. J Clin Invest 29:1326–35.

    Google Scholar 

  • Nakayama T, Mutsuga N, Tosato G (2007) FGF2 posttranscriptionally down-regulates expression of SDF1 in bone marrow stromal cells through FGFR1 IIIc. Blood 109:1363–72.

    Article  PubMed  CAS  Google Scholar 

  • Nibley WE, GJ S (1998) Primitive stem cells alone mediate rapid marrow recovery and multilineage engraftment after transplantation. Bone Marrow Tr 21:345–54.

    Article  CAS  Google Scholar 

  • Nilsson SK, Haylock D, Johnston H, Occhiodoro T, Brown T, Simmons PJ (2002) Hyaluronan is synthesized by primitive hemopoietic cells, participates in their lodgement at the endosteum following transplantation and is involved in the regulation of their proliferation and differentiation in vitro. Blood 101:856–62.

    Article  PubMed  CAS  Google Scholar 

  • Nilsson SK et al. (2005) Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106:1232–39.

    Article  PubMed  CAS  Google Scholar 

  • Nilsson SK, Simmons PJ (2004) Transplantable stem cells: home to specific niches. Curr Opin Hematol 11:102–06.

    Article  PubMed  Google Scholar 

  • Ogden DA, Mickliem HS (1976) The fate of serially transplanted bone marrow cell populations from young and old donors. Transplantation 22:287–93.

    Article  PubMed  CAS  Google Scholar 

  • Orlic D et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–05.

    Article  PubMed  CAS  Google Scholar 

  • Papayannopoulou T (2003) Bone marrow homing: the players, the playfield, and their evolving roles. Curr Opin Hematol 10:214–19.

    Article  PubMed  Google Scholar 

  • Papayannopoulou T (2004) Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization. Blood 103:1580–85.

    Article  PubMed  CAS  Google Scholar 

  • Papayannopoulou T, Priestley GV, Nakamoto B, Zafiropoulos V, Scott LM (2001) Molecular pathways in bone marrow homing: dominant role of alpha-4 Beta-1 over Beta-2-integrings and selectins. Blood 98:2403–11.

    Article  PubMed  CAS  Google Scholar 

  • Park IK, Morrison SJ, Clarke MF (2004) Bmi-1, stem cells, and senescence regulation. J Clin Invest 113:175–79.

    PubMed  CAS  Google Scholar 

  • Park IK et al. (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423:302–05.

    Article  PubMed  CAS  Google Scholar 

  • Peled A et al. (2000) The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 95:3289–96.

    PubMed  CAS  Google Scholar 

  • Penninx BWJ, Guralnik JM, Onder G, Ferrucci L, Wallace RB, Pahor M (2003) Anemia and decline in physical performance among older persons. Am J Med 115:104–10.

    Article  PubMed  Google Scholar 

  • Pinto A, Filippi RD, Frigeri F, Corazzelli G, Normanno N (2003) Ageing and the hemopoietic system. Crit Rev Oncol Hematol 48S:S3–S12.

    Article  Google Scholar 

  • Pruijt JF et al. (2002) Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice. Proc Natl Acad Sci USA 99:6228–33.

    Article  PubMed  CAS  Google Scholar 

  • Ramasamy R, Lam E, Soeiro I, Tisato V, Bonnet D, Dazzi F (2007) Mesencymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia 21:304–10.

    Article  PubMed  CAS  Google Scholar 

  • Ratajczak MZ, Reca R, Wysoczynksi M, Yan J, Ratajczak J (2006) Modulation of the SDF-1-CXCR4 axis by the third complement component (C3)-Implications for trafficking of CXCR4+ stem cells. Exp Hematol 34:986–95.

    Article  PubMed  CAS  Google Scholar 

  • Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–50.

    Article  PubMed  CAS  Google Scholar 

  • Rizo A, Vellenga E, de Haan G, Schuringa JJ (2006) Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche? Hum Mol Genet 15:210–19.

    Article  CAS  Google Scholar 

  • Roccaro AM et al. (2006) Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells. Cancer Res 66:184–91.

    Article  PubMed  CAS  Google Scholar 

  • Ross EA, Anderson N, Micklem HS (1982) Serial depletion and regeneration of the murine hematopoietic system. Implications for hematopoietic organization and the study of cellular ageing. J Exp Med 155:432–44.

    Article  PubMed  CAS  Google Scholar 

  • Ross J, Li L (2006) Recent advances in understanding extrinsic control of hematopoietic stem cell fate. Curr Opin Hematol 13:237–42.

    Article  PubMed  CAS  Google Scholar 

  • Rossi DJ, Bryder D, Weissman IL (2007) Hematopoietic stem cell ageing: Mechanism and consequence. Exp Gerontol in press.

    Google Scholar 

  • Rossi DJ et al. (2005) Cell intrinsic alterations underlie hematopoietic stem cell ageing. Proc Natl Acad Sci USA 102:9194–99.

    Article  PubMed  CAS  Google Scholar 

  • Rossi L et al. (2007) The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration. Blood 109:533–42.

    Article  PubMed  CAS  Google Scholar 

  • Sadighi A, AA, Miller R (2005) Signal transduction in the ageing immune system. Curr Opin Immunol 17:486–91.

    Article  CAS  Google Scholar 

  • Sauvageau G et al. (1994) Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc Natl Acad Sci USA 91:12223–27.

    Article  PubMed  CAS  Google Scholar 

  • Sauvageau G et al. (1995) Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev 9:1753–65.

    Article  PubMed  CAS  Google Scholar 

  • Savitsky K et al. (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268:1749–53.

    Article  PubMed  CAS  Google Scholar 

  • Schofield R (1978) The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4:7–25.

    PubMed  CAS  Google Scholar 

  • Schwartzberg LS et al. (1992) Peripheral blood stem cell mobilization by chemotherapy with and without recombinant human granulocyte colony-stimulating factor. J Hematother 1:317–27.

    PubMed  CAS  Google Scholar 

  • Siminovitch L, McCulloch EA, Till JE (1963) The distribution of colony-forming cells among spleen colonies. J Cell Compar Physiol 62:327–36.

    Article  CAS  Google Scholar 

  • Siminovitch L, Till JE, McCulloch EA (1964) Decline in colony-forming ability of marrow cells subjected to serial transplantation into irradiated mice. J Cell Physiol 64:23–31.

    Article  PubMed  CAS  Google Scholar 

  • Srour EF et al. (2001) Homing, cell cycle kinetics and fate of transplanted hematopoietic stem cells. Leukemia 15:1681–84.

    PubMed  CAS  Google Scholar 

  • Staal FJ, Clevers H (2005) WNT signalling and haematopoiesis: a WNT-WNT situation. Nat Rev Immunol 5:21–30.

    Article  PubMed  CAS  Google Scholar 

  • Stephan RP, Lill-Elghanian DA, Witte PL (1997) Development of B cells in aged mice: decline in the ability of pro-B cells to respond to IL-7 but not to other growth factors. J Immunol 158:1598–1609.

    PubMed  CAS  Google Scholar 

  • Stephan RP, Reilly CR, Witte PL (1998) Impaired ability of bone marrow stromal cells to support B-lymphopoiesis with age. Blood 91:75–88.

    PubMed  CAS  Google Scholar 

  • Stier S et al. (2005) Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. JEM 201:1781–91.

    Article  CAS  Google Scholar 

  • Sugiyama T, Kohara H, Noda M, Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25:977–88.

    Article  PubMed  CAS  Google Scholar 

  • Szilvassy SJ, Meyerrose TE, Ragland PL, B G (2001) Differential homing and engraftment properties of hematopoietic progenitor cells from murine bone marrow, mobilized peripheral blood, and fetal liver. Blood 98:2108–15.

    Google Scholar 

  • Szilvassy SJ, Ragland PL, Miller CL, Eaves CJ (2003) The marrow homing efficiency of murine hematopoietic stem cells remains constant during ontogeny. Exp Hematol 31:331–38.

    Article  PubMed  Google Scholar 

  • Taichman RS (2005) Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105:2631–39.

    Article  PubMed  CAS  Google Scholar 

  • Theise N (2006) Gastrointestinal stem cells. III. Emergent themes of liver stem cell biology: niche, quiescence, self-renewal, and plasticity. Am J Gastrointest Liver Physiol 290:G189–G193.

    Article  CAS  Google Scholar 

  • Thijssen DH et al. (2006) Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of ageing and training. Ageing Cell:495–503.

    Google Scholar 

  • Thomas J, Liu F, Link DC (2002) Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor. Curr Opin Hematol 9:183–89.

    Article  PubMed  Google Scholar 

  • Till JE, McCulloch EA (1961) A direct measurment of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14:213–22.

    Article  PubMed  CAS  Google Scholar 

  • Tyner SD et al. (2002) p53 mutant mice that display early ageing-associated phenotypes. Nature 415:45–53.

    Article  PubMed  CAS  Google Scholar 

  • Ueno H, Weissman IL (2006) Clonal analysis of mouse development reveals a polyclonal origin for yolk sac blood islands. Dev Cell 11:519–33.

    Article  PubMed  CAS  Google Scholar 

  • Van Zant G, Holland B, Eldridge P, Chen J-J (1990) Genotype-restricted growth and ageing patterns in hematopoietic stem cell populations of allophenic mice. J Exp Med 171:1547–65.

    Article  PubMed  Google Scholar 

  • Vartanian JP (2000) AMD-3100 (AnorMed). IDrugs 3:811–16.

    PubMed  CAS  Google Scholar 

  • Wagers AJ, Sherwood R, Christensen J, Weissman I (2002) Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297:2256–59.

    Article  PubMed  CAS  Google Scholar 

  • Walkley CR, Fero ML, Chien WM, Purton LE, McArthur GA (2005) Negative cell-cycle regulators cooperatively control self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol 7:172–78.

    Article  PubMed  CAS  Google Scholar 

  • Wang JC, Warner JK, Erdmann N, Lansdorp PM, Harrington L, Dick JE (2005) Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells. Proc Natl Acad Sci USA 102:14398–403.

    Article  PubMed  CAS  Google Scholar 

  • Wang X et al. (2003) Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422:897–901.

    Article  PubMed  CAS  Google Scholar 

  • Wilson A, Trump A (2006) Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6:93–106.

    Article  PubMed  CAS  Google Scholar 

  • Wright DE, Bowman EP, Wagers AJ, Butcher EC, Weissman IL (2002) Hematopoietic stem cells are uniquely selective in their migratory response to chemokines. J Exp Med 195:1145–54.

    Article  PubMed  CAS  Google Scholar 

  • Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL (2001) Physiological migration of hematopoietic stem and progenitor cells. Science 294.

    Google Scholar 

  • Xing Z et al. (2006) Increased hematopoietic stem cell mobilization in aged mice. Blood 108:2190–97.

    Article  PubMed  CAS  Google Scholar 

  • Yaniv I, Stein J, Farkas D, Askenasy N (2006) The tale of early hematopoietic cell seeding in the bone marrow niche. Stem Cells Dev 15:4–16.

    Article  PubMed  Google Scholar 

  • Yilmaz OH et al. (2006) Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441.

    Google Scholar 

  • Yu H, Yuan Y, Shen H, Cheng T (2006) Hematopoietic stem cell exhaustion impacted by p18 INK4C and p21 Cip1/Waf1 in opposite manners. Blood 107:1200–06.

    Article  PubMed  CAS  Google Scholar 

  • Yuan R, Astle C, Chen J, Harrison DE (2005) Genetic regulation of hematopoietic stem cell exhaustion during development and growth. Exp Hematol 33:243–50.

    Article  PubMed  Google Scholar 

  • Yuan Y, Shen H, Franklin DS, Scadden DT, Cheng T (2004) In vivo self-renewing divisions of haematopoietic stem cells are increased in the absence of the early G1-phase inhibitor, p18INK4C. Nature Cell Biol 6:436–42.

    Article  PubMed  CAS  Google Scholar 

  • Zeng H YR, Kosan C, Klein-Hitpass L, Moroy T. (2004) Transcription factor Gfi1 regulates self-renewal and engraftment of hematopoietic stem cells. EMBO J 23:4116–25.

    Article  PubMed  CAS  Google Scholar 

  • Zhang J et al. (2003) Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425:836–41.

    Article  PubMed  CAS  Google Scholar 

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Waterstrat, A., Oakley, E., Miller, A., Swiderski, C., Liang, Y., Van Zant, G. (2008). Mechanisms of Stem Cell Ageing. In: Rudolph, K.L. (eds) Telomeres and Telomerase in Ageing, Disease, and Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73709-4_6

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