Abstract
The haemopoietic stem cell (HSC) has long been regarded as an archetypal, tissue specific, stem cell, capable of completely regenerating haemopoiesis after myeloablation. It has proved relatively easy to harvest HSC, from bone marrow or peripheral blood. In turn, isolation of these cells has allowed therapeutic stem cell transplantation protocols to be developed, that capitalise on their prodigious self renewal and proliferative capabilities. Ex vivo approaches have been described to isolate, genetically manipulateand expand pluripotent stem cell subsets. These techniques have been crucial to the development of gene therapy, and may allow adults to enjoy the potential advantages of cord blood transplantation. Recently, huge conceptual changes have occurred in stem cell biology. In particular, the dogma that, in adults, stem cells are exclusively tissue restricted has been questioned and there is great excitement surrounding the potential plasticity of these cells, with the profound implications that this has, for developing novel cellular therapies. Mesenchymal stem cells, multipotent adult progenitor cells and embryonic stem cells are potential sources of cells for transplantation purposes. These cells may be directed toproduce HSC, in vitro and in the future may be used for therapeutic, or drug development, purposes.
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References
Abramson S, Miller RG & Phillips RA (1977) The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. J Exp Med 145: 1567–1579.
Aiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A, Morecki S, Andolfi G, Tabucchi A, Carlucci F, Marinello E, Cattaneo F, Vai S, Servida P, Miniero R, Roncarolo MG & Bordignon C (2002) Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296: 2410–2413.
Alcorn MJ, Farrell E, Barr J, Pearson C, Green R & Holyoake T (2000) The number of CD34+ cells mobilized into the peripheral blood can predict the quality of subsequent collections. J Hematother Stem Cell Res 9: 89–93.
Alcorn MJ & Holyoake TL (1996) Ex vivo expansion of haemopoietic progenitor cells. Blood Rev 10: 167–176.
Almeida-Porada G, Brown RL, MacKintosh FR & Zanjani ED (2000) Evaluation of serum-free culture conditions able to support the ex vivo expansion and engraftment of human hematopoietic stem cells in the human-to-sheep xenograft model. J Hematother Stem Cell Res 9: 683–693.
Andrews RG, Briddell RA, Knitter GH, Opie T, Bronsden M, Myerson D, Appelbaum FR & McNiece IK (1994) In vivo synergy between recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in baboons enhanced circulation of progenitor cells. Blood 84: 800–810.
Aversa F, Velardi A, Tabilio A, Reisner Y & Martelli MF (2001) Haploidentical stem cell transplantation in leukemia. Blood Rev 15: 111–119.
Bai L, Kon K, Tatsumi M, Ito H, Hayashi S & Brautigam M (2000) A human B-cell CLL model established by transplantation of JOK-1 cells into SCID mice and an anti-leukemia efficacy of fludarabine phosphate. Oncol Rep 7: 33–38.
Ball SE, Gibson FM, Rizzo S, Tooze JA, Marsh JC & Gordon-Smith EC (1998) Progressive telomere shortening in aplastic anemia. Blood 91: 3582–3592.
Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A & Hoffman R (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30: 42–48.
Baum CM, Weissman IL, Tsukamoto AS, Buckle AM & Peault B (1992) Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci USA 89: 2804–2808.
Bhardwaj G, Murdoch B, Wu D, Baker DP, Williams KP, Chadwick, K, Ling LE, Karanu FN & Bhatia M (2001) Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol 2: 172–180.
Bhatia M (2001) AC133 expression in human stem cells. Leukemia 15: 1685–1688.
Bhatia M, Bonnet D, Murdoch B, Gan OI & Dick JE (1998) A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat Med 4: 1038–1045.
Bhatia M, Bonnet D, Wu D, Murdoch B, Wrana J, Gallacher L & Dick JE (1999) Bone morphogenetic proteins regulate the developmental program of human hematopoietic stem cells. J Exp Med 189: 1139–1148.
Bhatia M, Wang JC, Kapp U, Bonnet D & Dick JE (1997a) Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci USA 94: 5320–5325.
Bhatia R, McGlave PB, Miller JS, Wissink S, Lin WN & Verfaillie CM (1997b) A clinically suitable ex vivo expansion culture system for LTC-IC and CFC using stroma-conditioned medium. Exp Hematol 25: 980–991.
Bittner RE, Schofer C, Weipoltshammer K, Ivanova S, Streubel B, Hauser E, Freilinger M, Hoger H, Elbe-Burger A & Wachtler F (1999) Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol (Berl) 199: 391–396.
Bonnet D & Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3: 730–737.
Bradford GB, Williams B, Rossi R & Bertoncello I (1997) Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp Hematol 25: 445–453.
Breems DA, Blokland EA, Siebel KE, Mayen AE, Engels LJ & Ploemacher RE (1998) Stroma-contact prevents loss of hematopoietic stem cell quality during ex vivo expansion of CD34+ mobilized peripheral blood stem cells. Blood 91: 111–117.
Brummendorf TH, Holyoake TL, Rufer N, Barnett MJ, Schulzer M, Eaves CJ, Eaves AC & Lansdorp PM (2000) Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry. Blood 95: 1883–1890.
Brummendorf TH, Rufer N, Baerlocher GM, Roosnek E & Lansdorp PM (2001a) Limited telomere shortening in hematopoietic stem cells after transplantation. Ann N Y Acad Sci 938: 1–7; discussion 7–8.
Brummendorf TH, Rufer N, Holyoake TL, Maciejewski J, Barnett MJ, Eaves CJ, Eaves AC, Young N & Lansdorp PM (2001b) Telomere length dynamics in normal individuals and in patients with hematopoietic stem cell-associated disorders. Ann N Y Acad Sci 938: 293–303; discussion 303–304.
Bunting KD (2002) ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells 20: 11–20.
Burt RK, Slavin S, Burns WH & Marmont AM (2002) Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: Getting closer to a cure? Blood 99: 768–784.
Cashman J, Clark-Lewis I, Eaves A & Eaves C (2002) Stromal derived factor 1 inhibits the cycling of very primitive human hematopoietic cells in vitro and in NOD/SCID mice. Blood 99: 792–799.
Castro RF, Jackson KA, Goodell MA, Robertson CS, Liu H & Shine HD (2002) Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science 297: 1299.
Caterson EJ, Nesti LJ, Danielson KG & Tuan RS (2002) Human marrow-derived mesenchymal progenitor cells: isolation, culture expansion, and analysis of differentiation. Mol Biotechnol 20: 245–256.
Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Deist FL & Fischer A (2000) Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288: 669–672.
Chakraverty R, Peggs K, Chopra R, Milligan DW, Kottaridis PD, Verfuerth S, Geary J, Thuraisundaram D, Branson K, Chakrabarti S, Mahendra P, Craddock C, Parker A, Hunter A, Hale G, Waldmann H, Williams CD, Yong K, Linch DC, Goldstone AH & Mackinnon S (2002) Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 99: 1071–1078.
Charbord P, Oostendorp R, Pang W, Herault O, Noel F, Tsuji T, Dzierzak E & Peault B (2002) Comparative study of stromal cell lines derived from embryonic, fetal, and postnatal mouse bloodforming tissues. Exp Hematol 30: 1202.
Chatta GS & Dale DC (1996) Aging and haemopoiesis. Implications for treatment with haemopoietic growth factors. Drugs Aging 9: 37–47.
Cheng T, Rodrigues N, Shen H, Yang Y, Dombkowski D, Sykes M & Scadden DT (2000) Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287: 1804–1808.
Cheshier SH, Morrison SJ, Liao X & Weissman IL (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci USA 96: 3120–3125.
Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitman S, Read EJ, Carter C, Bahceci E, Young NS & Barrett AJ (1999) Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: Full donor T-cell chimerism precedes alloimmune responses. Blood 94: 3234–3241.
Chiu CP, Dragowska W, Kim NW, Vaziri H, Yui J, Thomas TE, Harley CB & Lansdorp PM (1996) Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells 14: 239–248.
Civin CI, Almeida-Porada G, Lee MJ, Olweus J, Terstappen LW & Zanjani ED (1996) Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo. Blood 88: 4102–4109.
Corti S, Strazzer S, Del Bo R, Salani S, Bossolasco P, Fortunato F, Locatelli F, Soligo D, Moggio M, Ciscato P, Prelle A, Borsotti C, Bresolin N, Scarlato G & Comi GP (2002) A subpopulation of murine bone marrow cells fully differentiates along the myogenic pathway and participates in muscle repair in the mdx dystrophic mouse. Exp Cell Res 277: 74–85.
Craig W, Kay R, Cutler RL & Lansdorp PM (1993) Expression of Thy-1 on human hematopoietic progenitor cells. J Exp Med 177: 1331–1342.
Dao MA, Shah AJ, Crooks GM & Nolta JA (1998) Engraftment and retroviral marking of CD34+ and CD34+CD38– human hematopoietic progenitors assessed in immune-deficient mice. Blood 91: 1243–55.
Dennis JE, Carbillet JP, Caplan AI & Charbord P (2002) The STRO-1+ marrow cell population is multipotential. Cells Tissues Organs 170: 73–82.
Dexter TM, Moore MA & Sheridan AP (1977) Maintenance of hemopoietic stem cells and production of differentiated progeny in allogeneic and semiallogeneic bone marrow chimeras in vitro. J Exp Med 145: 1612–1616.
Dick JE (1996) Normal and leukemic human stem cells assayed in SCID mice. Semin Immunol 8: 197–206.
Dick JE, Sirard C, Pflumio F & Lapidot T (1992) Murine models of normal and neoplastic human haematopoiesis. Cancer Surv 15: 161–181.
Effros RB & Globerson A (2002) Hematopoietic cells and replicative senescence. Exp Gerontol 37: 191–196.
Engelhardt M & Finke J (2001) Does telomere shortening count? Blood 98: 888–890.
Engelhardt M, Kumar R, Albanell J, Pettengell R, Han W & Moore MA (1997) Telomerase regulation, cell cycle, and telomere stability in primitive hematopoietic cells. Blood 90: 182–193.
Erices A, Conget P & Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109: 235–242.
Evans MJ & Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154–156.
Facon T, Harousseau JL, Maloisel F, AttalM, Odriozola J, Alegre A, Schroyens W, Hulin C, Schots R, Marin P, Guilhot F, Granena A, DeWaele M, Pigneux A, Meresse V, Clark P & Reiffers J (1999) Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: A randomized, controlled trial. Blood 94: 1218–1225.
Flake AW (2001) In utero transplantation of haemopoietic stem cells. Best Pract Res Clin Haematol 14: 671–683.
Flake AW & Zanjani ED (1997) In utero hematopoietic stem cell transplantation. A status report. Jama 278: 932–937.
Flake AW & Zanjani ED (1998) In utero transplantation for thalassemia. Ann N Y Acad Sci 850: 300–311.
Flake AW & Zanjani ED (1999) In utero hematopoietic stem cell transplantation: Ontogenic opportunities and biologic barriers. Blood 94: 2179–2191.
Forbes SJ, Poulsom R & Wright NA (2002a) Hepatic and renal differentiation from blood-borne stem cells. Gene Ther 9: 625–630.
Forbes SJ, Vig P, Poulsom R, Wright NA & Alison MR (2002b) Adult stem cell plasticity: New pathways of tissue regeneration become visible. Clin Sci (Lond) 103: 355–369.
Friedberg JW, Neuberg D, Stone RM, Alyea E, Jallow H, LaCasce A, Mauch PM, Gribben JG, Ritz J, Nadler LM, Soiffer RJ & Freedman AS (1999) Outcome in patients with myelodysplastic syndrome after autologous bone marrow transplantation for non-Hodgkin's lymphoma. J Clin Oncol 17: 3128–3135.
Gallacher L, Murdoch B, Wu DM, Karanu FN, Keeney M & Bhatia M (2000) Isolation and characterization of human CD34(–)Lin(–) and CD34(+)Lin(–) hematopoietic stem cells using cell surface markers AC133 and CD7. Blood 95: 2813–2820.
Glaspy JA, Shpall EJ, LeMaistre CF, Briddell RA, Menchaca DM, Turner SA, Lill M, Chap L, Jones R, Wiers MD, Sheridan WP & McNiece IK (1997) Peripheral blood progenitor cell mobilization using stem cell factor in combination with filgrastim in breast cancer patients. Blood 90: 2939–2951.
Gluckman E (2001) Hematopoietic stem-cell transplants using umbilical-cord blood. N Engl J Med 344: 1860–1861.
Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, Ortega J, Souillet G, Ferreira E, Laporte JP, Fernandez M & Chastang C (1997) Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 337: 373–381.
Godin I & Cumano A (2002) The hare and the tortoise: An embryonic haematopoietic race. Nat Rev Immunol 2: 593–604.
Goldstone AH, Burnett AK, Wheatley K, Smith AG, Hutchinson RM & Clark RE (2001) Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood 98: 1302–1311.
Goodell MA (1999) Introduction: Focus on hematology. CD34(+) or CD34(–): does it really matter? Blood 94: 2545–2547.
Goodell MA, Rosenzweig M, Kim H, Marks DF, DeMaria M, Paradis G, Grupp SA, Sieff CA, Mulligan RC & Johnson RP (1997) Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med 3: 1337–1345.
Graf T (2002) Differentiation plasticity of hematopoietic cells. Blood 99: 3089–3101.
Graham GJ & Pragnell IB (1992) The haemopoietic stem cell: Properties and control mechanisms. Semin Cell Biol 3: 423–434.
Graham GJ & Wright EG (1997) Haemopoietic stem cells: Their heterogeneity and regulation. Int J Exp Pathol 78: 197–218.
Graham SM, Jorgensen HG, Allan E, Pearson C, Alcorn MJ, Richmond L & Holyoake TL (2002) Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 99: 319–325.
Grant MB, May WS, Caballero S, Brown GA, Guthrie SM, Mames RN, Byrne BJ, Vaught T, Spoerri PE, Peck AB & Scott EW (2002) Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med 8: 607–612.
Gratwohl A, Passweg J, Gerber I & Tyndall A (2001) Stem cell transplantation for autoimmune diseases. Best Pract Res Clin Haematol 14: 755–776.
Greider CW (1994) Mammalian telomere dynamics: Healing, fragmentation shortening and stabilization. Curr Opin Genet Dev 4: 203–211.
Grompe M (2002) Adult versus Embryonic Stem Cells: It's Still a Tie. Mol Ther 6: 303.
Gunzburg W, Hemiston T, Seymour L (eds) (2002) Gene transfer and cell based therapies. Current opinion in molecular therapeutics 4: 281–407.
Hackney JA, Charbord P, Brunk BP, Stoeckert CJ, Lemischka IR & Moore KA (2002) A molecular profile of a hematopoietic stem cell niche. Proc Natl Acad Sci USA 99: 13061–13066.
Hall FL, Han B, Kundu RK, Yee A, Nimni ME & Gordon EM (2001) Phenotypic differentiation of TGF-beta1-responsive pluripotent premesenchymal prehematopoietic progenitor (P4 stem) cells from murine bone marrow. J Hematother Stem Cell Res 10: 261–271.
Hao QL, Thiemann FT, Petersen D, Smogorzewska EM & Crooks GM (1996) Extended long-term culture reveals a highly quiescent and primitive human hematopoietic progenitor population. Blood 88: 3306–3313.
Harrison DE (1979) Mouse erythropoietic stem cell lines function normally 100 months: loss related to number of transplantations. Mech Ageing Dev 9: 427–433.
Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hackett NR, Crystal RG, Moore MA, Werb Z Lyden D & Rafii S (2002) Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 8: 841–849.
Hayashi S, Peranteau WH, Shaaban AF & Flake AW (2002) Complete allogeneic hematopoietic chimerism achieved by a combined strategy of in utero hematopoietic stem cell transplantation and postnatal donor lymphocyte infusion. Blood 100: 804–812.
Hayflick L (1992) Aging, longevity, and immortality in vitro. Exp Gerontol 27: 363–368.
Hayward A, Ambruso D, Battaglia F, Donlon T, Eddelman K, Giller R, Hobbins J, Hsia YE, Quinones R, Shpall E, Trachtenberg E & Giardina P (1998) Microchimerism and tolerance following intrauterine transplantation and transfusion for alphathalassemia-1. Fetal Diagn Ther 13: 8–14.
Heike T & Nakahata T (2002) Ex vivo expansion of hematopoietic stem cells by cytokines. Biochim Biophys Acta 1592: 313–321.
Henslee-Downey PJ (2001) Allogeneic transplantation across major HLA barriers. Best Pract Res Clin Haematol 14: 741–754.
Hess DA, Levac KD, Karanu FN, Rosu-Myles M, White MJ, Gallacher L, Murdoch B, Keeney M, Ottowski P, Foley R, Chin-Yee I & Bhatia M (2002) Functional analysis of human hematopoietic repopulating cells mobilized with granulocyte colonystimulating factor alone versus granulocyte colony-stimulating factor in combination with stem cell factor. Blood 100: 869–878.
Heyworth C, Pearson S, May G & Enver T (2002) Transcription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells. Embo J 21: 3770–3781.
Hirschi KK & Goodell MA (2002) Hematopoietic, vascular and cardiac fates of bone marrow-derived stem cells. Gene Ther 9: 648–652.
Hole N & Graham GJ (1997) Use of embryonal stem cells in studies of molecular haemopoiesis. Baillieres Clin Haematol 10: 467–483.
Hole N, Graham GJ, Menzel U & Ansell JD (1996) A limited temporal window for the derivation of multilineage repopulating hematopoietic progenitors during embryonal stem cell differentiation in vitro. Blood 88: 1266–1276.
Holyoake T, Jiang X, Eaves C & Eaves A (1999a) Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood 94: 2056–2064.
Holyoake TL (1996) Cytokines at the research-clinical interface: Potential applications. Blood Rev 10: 189–200.
Holyoake TL, Alcorn MJ, Richmond L, Farrell E, Pearson C, Green R, Dunlop DJ, Fitzsimons E, Pragnell IB & Franklin IM (1997) CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens. Bone Marrow Transplant 19: 1095–1101.
Holyoake TL, Freshney MG, Konwalinka G, Haun M, Petzer A, Fitzsimons E, Lucie NP, Wright EG & Pragnell IB (1993) Mixed colony formation in vitro by the heterogeneous compartment of multipotential progenitors in human bone marrow. Leukemia 7: 207–213.
Holyoake TL, Freshney MG, McNair L, Parker AN, McKay PJ, Steward WP, Fitzsimons E, Graham GJ & Pragnell IB (1996) Ex vivo expansion with stem cell factor and interleukin-11 augments both short-term recovery posttransplant and the ability to serially transplant marrow. Blood 87: 4589–4595.
Holyoake TL, Jiang X, Jorgensen HG, Graham S, Alcorn MJ, Laird C, Eaves AC & Eaves CJ (2001) Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor-independent growth in vitro in association with upregulation of expression of interleukin-3. Blood 97: 720–728.
Holyoake TL, Nicolini FE & Eaves CJ (1999b) Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow. Exp Hematol 27: 1418–1427.
Horwitz EM (2001) Marrow mesenchymal cell transplantation for genetic disorders of bone. Cytotherapy 3: 399–401.
Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L & Hofmann T (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci USA 99: 8932–8937.
Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE & Brenner MK (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5: 309–313.
Horwitz EM, Prockop DJ, Gordon PL, Koo WW, Fitzpatrick LA, Neel MD, McCarville ME, Orchard PJ, Pyeritz RE & Brenner MK (2001) Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood 97: 1227–1231.
Ishikawa F, Livingston AG, Wingard JR, Nishikawa S & Ogawa M (2002) An assay for long-term engrafting human hematopoietic cells based on newborn NOD/SCID/beta2-microglobulin(null) mice. Exp Hematol 30: 488–494.
Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, Ueyama Y, Koyanagi Y, Sugamura K, Tsuji K, Heike T & Nakahata T (2002) NOD/SCID/gamma(c)(null) mouse: An excellent recipient mouse model for engraftment of human cells. Blood 100: 3175–3182.
Ito T, Tajima F & Ogawa M (2000) Developmental changes of CD34 expression by murine hematopoietic stem cells. Exp Hematol 28: 1269–1273.
Jackson KA, Mi T & Goodell MA (1999) Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci USA 96: 14482–14486.
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA & Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41–49.
Jones DR, Bui TH, Anderson EM, Ek S, Liu D, Ringden O & Westgren M (1996) In utero haematopoietic stem cell transplantation: current perspectives and future potential. Bone Marrow Transplant 18: 831–837.
Jordan CT & Lemischka IR (1990) Clonal and systemic analysis of long-term hematopoiesis in the mouse. Genes Dev 4: 220–232.
Jørgensen H, Allan E, Graham S, Richmond L, Godden J & Holyoake T (2002a) Will drug combinations effectively eradicate quiescent leukaemic stem cells in Chronic Myeloid Leukaemia. Experimental Hematology 30: 73.
Jørgensen HG, Elliott MA, Allan EK, Carr CE, Holyoake TL & Smith KD (2002b) Alpha-1-acid glycoprotein expressed in the plasma of chronic myeloid leukaemia patients does not mediate significant in vitro resistance to STI571 (Glivec). Blood 99: 713–715.
Jørgensen HG, Elliott MA, Paterson S, Holyoake TL & Smith KD (2002c) Further observations on the debated ability of AGP to bind imatinib. Blood 100: 368–369.
Kawashima I, Zanjani ED, Almaida-Porada G, Flake AW, Zeng H & Ogawa M (1996) CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrowengrafting cells. Blood 87: 4136–4142.
Kay MA, Manno CS, Ragni MV, Larson PJ, Couto LB, McClelland A, Glader B, Chew AJ, Tai SJ, Herzog RW, Arruda V, Johnson F, Scallan C, Skarsgard E, Flake AW & High KA (2000) Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet 24: 257–261.
Keller G & Snodgrass HR (1999) Human embryonic stem cells: The future is now. Nat Med 5: 151–152.
Keller G & Snodgrass R (1990) Life span of multipotential hematopoietic stem cells in vivo. J Exp Med 171: 1407–1418.
Keller GM (1995) In vitro differentiation of embryonic stem cells. Curr Opin Cell Biol 7: 862–869.
Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernaute R, Bankiewicz K & McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418: 50–56.
Koc ON & Lazarus HM (2001) Mesenchymal stem cells: Heading into the clinic. Bone Marrow Transplant 27: 235–239.
Kojika S & Griffin JD (2001) Notch receptors and hematopoiesis. Exp Hematol 29: 1041–1052.
Kollet O, Peled A, Byk T, Ben-Hur H, Greiner D, Shultz L & Lapidot T (2000) beta2 microglobulin-deficient (B2m(null)) NOD/SCID mice are excellent recipients for studying human stem cell function. Blood 95: 3102–3105.
Korbling M (1997) Peripheral blood stem cells: A novel source for allogeneic transplantation. Oncologist 2: 104–113.
Korbling M & Anderlini P (2001) Peripheral blood stem cell versus bone marrow allotransplantation: Does the source of hematopoietic stem cells matter? Blood 98: 2900–2908.
Korbling M, Katz RL, Khanna A, Ruifrok AC, Rondon G, Albitar M, Champlin RE & Estrov Z (2002) Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Engl J Med 346: 738–746.
Krause DS (2002) Plasticity of marrow-derived stem cells. Gene Ther 9: 754–758.
Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL & Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6: 1229–1234.
Lane TA, Ho AD, Bashey A, Peterson S, Young D & Law P (1999) Mobilization of blood-derived stem and progenitor cells in normal subjects by granulocyte-macrophage-and granulocytecolony-stimulating factors. Transfusion 39: 39–47.
Larochelle A, Vormoor J, Hanenberg H, Wang JC, Bhatia M, Lapidot T, Moritz T, Murdoch B, Xiao XL, Kato I, Williams DA & Dick JE (1996) Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy. Nat Med 2: 1329–1337.
Lataillade JJ, Clay D, Bourin P, Herodin F, Dupuy C, Jasmin C & Bousse-Kerdiles MC (2002) Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(1) transition in CD34(+) cells: Evidence for an autocrine/paracrine mechanism. Blood 99: 1117–1129.
Le Bousse-Kerdiles MC, Chevillard S, Charpentier A, Romquin N, Clay D, Smadja-Joffe F, Praloran V, Dupriez B, Demory JL, Jasmin C & Martyre MC (1996) Differential expression of transforming growth factor-beta, basic fibroblast growth factor, and their receptors in CD34+ hematopoietic progenitor cells from patients with myelofibrosis and myeloid metaplasia. Blood 88: 4534–4546.
Lee HW, Blasco MA, Gottlieb GJ, Horner JW, 2nd Greider CW & DePinho RA (1998) Essential role of mouse telomerase in highly proliferative organs. Nature 392: 569–574.
Lemischka I (2001) Stem cell dogmas in the genomics era. Rev Clin Exp Hematol 5: 15–25.
Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN & Simmons PJ (2001) Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood 98: 1289–1297.
Liu F, Poursine-Laurent J & Link DC (1997) The granulocyte colony-stimulating factor receptor is required for the mobilization of murine hematopoietic progenitors into peripheral blood by cyclophosphamide or interleukin-8 but not flt-3 ligand. Blood 90: 2522–2528.
Liu F, Poursine-Laurent J & Link DC (2000) Expression of the GCSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF. Blood 95: 3025–3031.
Loeuillet C, Bernard G, Remy-Martin J, Saas P, Herve P, Douay L & Chalmers D (2001) Distinct hematopoietic support by two human stromal cell lines. Exp Hematol 29: 736–745.
Mackenzie TC, Shaaban AF, Radu A & Flake AW (2002) Engraftment of bone marrow and fetal liver cells after in utero transplantation in MDX mice. J Pediatr Surg 37: 1058–1064.
Mahmud N, Devine SM, Weller KP, Parmar S, Sturgeon C, Nelson MC, Hewett T & Hoffman R (2001) The relative quiescence of hematopoietic stem cells in nonhuman primates. Blood 97: 3061–3068.
Maris M, Woolfrey A, McSweeney PA, Sandmaier BM, Nash RA, Georges G, Maloney DG, Molina A, Chauncey T, Yu C, Zaucha JM, Blume KG, Shizuru J, Niederwieser D & Storb R (2001) Nonmyeloablative hematopoietic stem cell transplantation: Transplantation for the 21st century. Front Biosci 6: G13–G16.
Marshall E (2000) The business of stem cells. Science 287: 1419–1421.
Marshall E (2002a) Clinical research. Gene therapy a suspect in leukemia-like disease. Science 298: 34–35.
Marshall E (2002b) Gene therapy. What to do when clear success comes with an unclear risk? Science 298: 510–511.
Mathioudakis G, Storb R, McSweeney PA, Torok-Storb B, Lansdorp PM, Brummendorf T, Gass MJ, Bryant EM, Storek J, Flowers ME, Gooley T & Nash RA (2000) Polyclonal hematopoiesis with variable telomere shortening in human long-term allogeneic marrow graft recipients. Blood 96: 3991–3994.
Mavroudis D, Read E, Cottler-Fox M, Couriel D, Molldrem J, Carter C, Yu M, Dunbar C & Barrett J (1996) CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies. Blood 88: 3223–3229.
McKay R (2002) Building animals from stem cells. Ann N Y Acad Sci, 961: 44.
McKinney-Freeman SL, Jackson KA, Camargo FD, Ferrari G, Mavilio F & Goodell MA (2002) Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci USA 99: 1341–1346.
Mezey E, Chandross KJ, Harta G, Maki RA & McKercher SR (2000) Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow. Science 290: 1779–1782.
Migliaccio AR, Adamson JW, Stevens CE, Dobrila NL, Carrier CM & Rubinstein P (2000) Cell dose and speed of engraftment in placental/umbilical cord blood transplantation: Graft progenitor cell content is a better predictor than nucleated cell quantity. Blood 96: 2717–2722.
Milner LA & Bigas A (1999) Notch as a mediator of cell fate determination in hematopoiesis: Evidence and speculation. Blood 93: 2431–2448.
Molineux G, Migdalska A, Szmitkowski M, Zsebo K & Dexter TM (1991) The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor. Blood 78: 961–966.
Molineux G, Pojda Z, Hampson IN, Lord BI & Dexter TM (1990) Transplantation potential of peripheral blood stem cells induced by granulocyte colony-stimulating factor. Blood 76: 2153–2158.
Monahan PE & White IG (2002) Hemophilia gene therapy: Update. Curr Opin Hematol 9: 430–436.
Moore KA, Ema H & Lemischka IR (1997) In vitro maintenance of highly purified, transplantable hematopoietic stem cells. Blood 89: 4337–4347.
Moore MA, Hattori K, Heissig B, Shieh JH, Dias S, Crystal RG & Rafii S (2001) Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1: VEGF, and angiopoietin-1. Ann N Y Acad Sci 938: 36–45; discussion 45–47.
Morrison SJ, Prowse KR, Ho P & Weissman IL (1996a) Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5: 207–216.
Morrison SJ, Shah NM & Anderson DJ (1997) Regulatory mechanisms in stem cell biology. Cell 88: 287–298.
Morrison SJ, Wandycz AM, Akashi K, Globerson A & Weissman IL (1996b) The aging of hematopoietic stem cells. Nat Med 2: 1011–1016.
Moskowitz CH, Stiff P, Gordon MS, McNiece I, Ho AD, Costa JJ, Broun ER, Bayer RA, Wyres M, Hill J, Jelaca-Maxwell K, Nichols CR, Brown SL, Nimer SD & Gabrilove J (1997) Recombinant methionyl human stem cell factor and filgrastim for peripheral blood progenitor cell mobilization and transplantation in non-Hodgkin's lymphoma patients–resultsof a phase I/II trial. Blood 89: 3136–3147.
Murray L, Chen B, Galy A, Chen S, Tushinski R, Uchida N, Negrin R, Tricot G, Jagannath S, Vesole D et al. (1995) Enrichment of human hematopoietic stem cell activity in the CD34 + Thy-1 + Lin-subpopulation from mobilized peripheral blood. Blood 85: 368–378.
Nichols J (2001) Introducing embryonic stem cells. Curr Biol 11: R503–R505.
Nijmeijer BA, Mollevanger P, van Zelderen-Bhola SL, Kluin-Nelemans HC, Willemze R & Falkenburg JH (2001) Monitoring of engraftment and progression of acute lymphoblastic leukemia in individual NOD/SCID mice. Exp Hematol 29: 322–329.
Nijmeijer BA, Willemze R & Falkenburg JH (2002) An animal model for human cellular immunotherapy: specific eradication of human acute lymphoblastic leukemia by cytotoxic T lymphocytes in NOD/scid mice. Blood 100: 654–660.
Odorico JS, Kaufman DS & Thomson JA (2001) Multilineage differentiation from human embryonic stem cell lines. Stem Cells 19: 193–204.
Okamoto R, Yajima T, Yamazaki M, Kanai T, Mukai M, Okamoto S, Ikeda Y, Hibi T, Inazawa J & Watanabe M (2002) Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract. Nat Med 8: 1011–1017.
Oostendorp RA, Harvey KN, Kusadasi N, de Bruijn MF, Saris C, Ploemacher RE, Medvinsky AL & Dzierzak EA (2002) Stromal cell lines from mouse aorta-gonads-mesonephros subregions are potent supporters of hematopoietic stem cell activity. Blood 99: 1183–1189.
Orkin SH & Morrison SJ (2002) Stem-cell competition. Nature 418: 25–27.
Orkin SH & Zon LI (2002) Hematopoiesis and stem cells: Plasticity versus developmental heterogeneity. Nat Immunol 3: 323–328.
Osawa M, Hanada K, Hamada H & Nakauchi H (1996) Longterm lymphohematopoietic reconstitution by a single CD34–low/negative hematopoietic stem cell. Science 273: 242–245.
Oscier DG (1987) Myelodysplastic syndromes. Baillieres Clin Haematol 1: 389–426.
Palacios R, Golunski E & Samaridis J (1995) In vitro generation of hematopoietic stem cells from an embryonic stem cell line. Proc Natl Acad Sci USA 92: 7530–7534.
Papayannopoulou T & Nakamoto B (1993) Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin. Proc Natl Acad Sci USA 90: 9374–9378.
Papayannopoulou T, Priestley GV & Nakamoto B (1998) Anti-VLA4/VCAM-1-induced mobilization requires cooperative signaling through the kit/mkit ligand pathway. Blood 91: 2231–2239.
Papayannopoulou T, Priestley GV, Nakamoto B, Zafiropoulos V, Scott LM & Harlan JM (2001) Synergistic mobilization of hemopoietic progenitor cells using concurrent beta1 and beta2 integrin blockade or beta2-deficient mice. Blood 97: 1282–1288.
Pecora AL, Preti RA, Gleim GW, Jennis A, Zahos K, Cantwell S, Doria L, Isaacs R, Gillio AP, Michelis MA & Brochstein JA (1998) CD34+CD33– cells influence days to engraftment and transfusion requirements in autologous blood stem-cell recipients. J Clin Oncol 16: 2093–2104.
Peschle C, Botta R, Muller R, Valtieri M & Ziegler BL (2001) Purification and functional assay of pluripotent hematopoietic stem cells. Rev Clin Exp Hematol 5: 3–14.
Petzer AL, Zandstra PW, Piret JM & Eaves CJ (1996) Differential cytokine effects on primitive (CD34+CD38-) human hematopoietic cells: Novel responses to Flt3-ligand and thrombopoietin. J Exp Med 183: 2551–2558.
Piacibello W, Sanavio F, Garetto L, Severino A, Bergandi D, Ferrario J, Fagioli F, Berger M & Aglietta M (1997) Extensive amplification and self-renewal of human primitive hematopoietic stem cells from cord blood. Blood 89: 2644–2653.
Pilarski LM & Belch AR (2002) Clonotypic myeloma cells able to xenograft myeloma to nonobese diabetic severe combined immunodeficient mice copurify with CD34(+) hematopoietic progenitors. Clin Cancer Res 8: 3198–3204.
Pilarski LM, Seeberger K, Coupland RW, Eshpeter A, Keats JJ, Taylor BJ & Belch AR (2002) Leukemic B cells clonally identical to myeloma plasma cells are myelomagenic in NOD/SCID mice. Exp Hematol 30: 221–228.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S & Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147.
Ploemacher RE (1999) Characterisation and biology of normal human haematopoietic stem cells. Haematologica, 84 Suppl EHA 4: 4–7.
Podesta M, Piaggio G, Frassoni F, Pitto A, Mordini N, Bregante S, Valeriani A & Bacigalupo A (1997) Deficient reconstitution of early progenitors after allogeneic bone marrow transplantation. Bone Marrow Transplant 19: 1011–1017.
Podesta M, Piaggio G, Frassoni F, Pitto A, Zikos P, Sessarego M, Abate M, Teresa Van Lint M, Berisso G & Bacigalupo A (1998) The assessment of the hematopoietic reservoir after immunosuppressive therapy or bone marrow transplantation in severe aplastic anemia. Blood 91: 1959–1965.
Potocnik AJ, Nielsen PJ & Eichmann K (1994) In vitro generation of lymphoid precursors from embryonic stem cells. Embo J 13: 5274–5283.
Powles R, Mehta J, Kulkarni S, Treleaven J, Millar B, Marsden J, Shepherd V, Rowland A, Sirohi B, Tait D, Horton C, Long S & Singhal S (2000) Allogeneic blood and bone-marrow stemcell transplantation in haematological malignant diseases: A randomised trial. Lancet 355: 1231–1237.
Pratt G, Rawstron AC, English AE, Johnson RJ, Jack AS, Morgan GJ & Smith GM (2001) Analysis of CD34+ cell subsets in stem cell harvests can more reliably predict rapidity and durability of engraftment than total CD34+ cell dose, but steady state levels do not correlate with bone marrow reserve. Br J Haematol 114: 937–943.
Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276: 71–74.
Prosper F, Stroncek D & Verfaillie CM (1996) Phenotypic and functional characterization of long-term culture-initiating cells present in peripheral blood progenitor collections of normal donors treated with granulocyte colony-stimulating factor. Blood 88: 2033–2042.
Punzel M, Gupta P, Roodell M, Mortari F & Verfaillie CM (1999a) Factor(s) secreted by AFT024 fetal liver cells following stimulation with human cytokines are important for human LTC-IC growth. Leukemia 13: 1079–1084.
Punzel M, Moore KA, Lemischka IR & Verfaillie CM (1999b) The type of stromal feeder used in limiting dilution assays influences frequency and maintenance assessment of human long-term culture initiating cells. Leukemia 13: 92–97.
Punzel M, Wissink SD, Miller JS, Moore KA, Lemischka IR & Verfaillie CM (1999c) The myeloid-lymphoid initiating cell (MLIC) assay assesses the fate of multipotent human progenitors in vitro. Blood 93: 3750–3756.
Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L & Verfaillie CM (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98: 2615–2625.
Reyes M & Verfaillie CM (2001) Characterization of multipotent adult progenitor cells, a subpopulation of mesenchymal stem cells. Ann N Y Acad Sci 938: 231–233; discussion 233–235.
Risau W, Sariola H, Zerwes HG, Sasse J, Ekblom P, Kemler R & Doetschman T (1988) Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 102: 471–478.
Robertson JA (2001) Human embryonic stem cell research: Ethical and legal issues. Nat Rev Genet 2: 74–78.
Roeder I & Loeffler M (2002) A novel dynamic model of hematopoietic stem cell organization based on the concept of within tissue plasticity. Exp Hematol 30: 853–861.
Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR, Berkowitz RL, Cabbad M, Dobrila NL, Taylor PE, Rosenfield RE & Stevens CE (1998) Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 339: 1565–1577.
Rufer N, Brummendorf TH, Chapuis B, Helg C, Lansdorp PM & Roosnek E (2001) Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation. Blood 97: 575–577.
Rufer N, Brummendorf TH, Kolvraa S, Bischoff C, Christensen K, Wadsworth L, Schulzer M & Lansdorp PM (1999) Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med 190: 157–167.
Sanchez-Ramos JR (2002) Neural cells derived from adult bone marrow and umbilical cord blood. J Neurosci Res 69: 880–893.
Sato T, Laver JH & OgawaM(1999) Reversible expression of CD34 by murine hematopoietic stem cells. Blood 94: 2548–2554.
Schofield R (1978) The relationship between the spleen colonyforming cell and the haemopoietic stem cell. Blood Cells 4: 7–25.
Shay JW (1998) Accelerated telomere shortening in bone-marrow recipients. Lancet 351: 153–154.
Shay JW & Wright WE (2000) Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol 1: 72–76.
Shultz LD, Lang PA, Christianson SW, Gott B, Lyons B, Umeda S, Leiter E, Hesselton R, Wagar EJ, Leif JH, Kollet O, Lapidot T & Greiner DL (2000) NOD/LtSz-Rag1null mice: An immunodeficient and radioresistant model for engraftment of human hematolymphoid cells, HIV infection, and adoptive transfer of NOD mouse diabetogenic T cells. J Immunol 164: 2496–2507.
Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B, McKenna S, Mobraaten L, Rajan TV, Greiner DL et al. (1995) Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol 154: 180–191.
Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A & Or R (1998) Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91: 756–763.
Smith AG (2001) Embryo-derived stem cells: Of mice and men. Annu Rev Cell Dev Biol 17: 435–462.
Storb R, Yu C, Sandmaier BM, McSweeney PA, Georges G, Nash RA & Woolfrey A (1999) Mixed hematopoietic chimerism after marrow allografts. Transplantation in the ambulatory care setting. Ann N Y Acad Sci 872: 372-375; discussion 375–376.
Sutherland HJ, Eaves CJ, Eaves AC, Dragowska W & Lansdorp PM (1989) Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood 74: 1563–1570.
Szilvassy SJ, Meyerrose TE & Grimes B (2000) Effects of cell cycle activation on the short-term engraftment properties of ex vivo expanded murine hematopoietic cells. Blood 95: 2829–2837.
Tabbara IA, Zimmerman K, Morgan C & Nahleh Z (2002) Allogeneic hematopoietic stem cell transplantation: complications and results. Arch Intern Med 162: 1558–1566.
Takeuchi M, Sekiguchi T, Hara T, Kinoshita T & Miyajima A (2002) Cultivation of aorta-gonad-mesonephros-derived hematopoietic stem cells in the fetal liver microenvironment amplifies longterm repopulating activity and enhances engraftment to the bone marrow. Blood 99: 1190–1196.
Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE & Scott EW (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416: 542–545.
Terstappen LW, Huang S, Safford M, Lansdorp PM & Loken MR (1991) Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38– progenitor cells. Blood 77: 1218–1227.
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS & Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147.
Thomson JA & Marshall VS (1998) Primate embryonic stem cells. Curr Top Dev Biol 38: 133–165.
Thornley I, Sutherland DR, Nayar R, Sung L, Freedman MH & Messner HA (2001) Replicative stress after allogeneic bone marrow transplantation: changes in cycling of CD34+CD90+ and CD34+CD90– hematopoietic progenitors. Blood 97: 1876–1878.
Tisdale JF & Wilson DR (eds) (2002) Clinical applications of gene therapy. Current Opinion in Molecular Therapeutics, 4: 409–534.
Traycoff CM, Hoffman R, Zanjani ED, Cornetta K, Law P, Gianni AM, Bregni M, Siena S, Abboud MR, Laver J et al. (1994) Measurement of marrow repopulating potential of human hematopoietic progenitor and stem cells using a fetal sheep model. Prog Clin Biol Res 389: 281–291.
Tsai RY, Kittappa R & McKay RD (2002) Plasticity, niches, and the use of stem cells. Dev Cell 2: 707–712.
Turner CW, Yeager AM, Waller EK, Wingard JR & Fleming WH (1996) Engraftment potential of different sources of human hematopoietic progenitor cells in BNX Mice. Blood 87: 3237–3244.
Ueda T, Yoshino H, Kobayashi K, Kawahata M, Ebihara Y, Ito M, Asano S, Nakahata T & Tsuji K (2000) Hematopoietic repopulating ability of cord blood CD34(+) cells in NOD/Shi-scid mice. Stem Cells 18: 204–213.
Van Den Berg DJ, Sharma AK, Bruno E & Hoffman R (1998) Role of members of the Wnt gene family in human hematopoiesis. Blood 92: 3189–3202.
Vassiliou G, Amrolia P & Roberts IA (2001) Allogeneic transplantation for haemoglobinopathies. Best Pract Res Clin Haematol 14: 807–822.
Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB & Lansdorp PM (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci USA 91: 9857–9860.
Verfaillie CM, Almeida-Porada G, Wissink S & Zanjani ED (2000) Kinetics of engraftment of CD34(–) and CD34(+) cells from mobilized blood differs from that of CD34(–) and CD34(+) cells from bone marrow. Exp Hematol 28: 1071–1079.
Wagers AJ, Sherwood RI, Christensen JL & Weissman IL (2002) Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297: 2256–2259.
Wang JC, Lapidot T, Cashman JD, Doedens M, Addy L, Sutherland DR, Nayar R. Laraya P, Minden M, Keating A, Eaves AC, Eaves CJ & Dick JE (1998) High level engraftment of NOD/SCID mice by primitive normal and leukemic hematopoietic cells from patients with chronic myeloid leukemia in chronic phase. Blood 91: 2406–2414.
Weaver A, Ryder D, Crowther D, Dexter TM & Testa NG (1996) Increased numbers of long-term culture-initiating cells in the apheresis product of patients randomized to receive increasing doses of stem cell factor administered in combination with chemotherapy and a standard dose of granulocyte colonystimulating factor. Blood 88: 3323–3328.
Wiles MV & Keller G (1991) Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development 111: 259–267.
Woods NB, Ooka A & Karlsson S (2002) Development of gene therapy for hematopoietic stem cells using lentiviral vectors. Leukemia 16: 563–569.
Wynn R, Thornley I, Freedman M & Saunders EF (1999) Telomere shortening in leucocyte subsets of long-term survivors of allogeneic bone marrow transplantation. Br J Haematol 105: 997–1001.
Wynn RF, Cross MA, Hatton C, Will AM, Lashford LS, Dexter TM & Testa NG (1998) Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants. Lancet 351: 178–181.
Yamashita J, Itoh H, Hirashima M, Ogawa M, Nishikawa S, Yurugi T, Naito M & Nakao K (2000) Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408: 92–96.
Yan XQ, Hartley C, McElroy P, Chang A, McCrea C & McNiece I (1995) Peripheral blood progenitor cells mobilized by recombinant human granulocyte colony-stimulating factor plus recombinant rat stem cell factor contain long-term engrafting cells capable of cellular proliferation for more than two years as shown by serial transplantation in mice. Blood 85: 2303–2307.
Ying QL, Nichols J, Evans EP & Smith AG (2002) Changing potency by spontaneous fusion. Nature 416: 545–548.
Zanjani ED, Ascensao JL, Flake AW, Harrison MR & Tavassoli M (1992) The fetus as an optimal donor and recipient of hemopoietic stem cells. Bone Marrow Transplant 10: 107–114.
Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H & Sorrentino BP (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7: 1028–1034.
Ziegler BL, Valtieri M, Porada GA, De Maria R, Muller R, Masella B, Gabbianelli M, Casella I, Pelosi E, Bock T, Zanjani ED & Peschle C (1999) KDR receptor: A key marker defining hematopoietic stem cells. Science 285: 1553–1558.
Zon LI (1995) Developmental biology of hematopoiesis. Blood 86: 2876–2891.
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Clark, A.D., Jørgensen, H.G., Mountford, J. et al. Isolation and therapeutic potential of human haemopoietic stem cells. Cytotechnology 41, 111–131 (2003). https://doi.org/10.1023/A:1024822722285
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DOI: https://doi.org/10.1023/A:1024822722285