In the past decade, we have witnessed significant advances in ex vivo hematopoietic stem cell culture expansion, progressing to the point where clinical trials are being designed and conducted. Preclinical milestone investigations provided data to enable expansion of portions of hematopoietic grafts in a clinical setting, indicating safety and feasibility of this approach. Data derived from current clinical trials indicate successful reconstitution of hematopoiesis after myeloablative chemoradiotherapy using infusion of ex vivo-expanded perfusion cultures. Future avenues of exploration will focus upon refining preclinical and clinical studies in which cocktails of available cytokines, novel molecules and sophisticated expansion systems will explore expansion of blood, marrow and umbilical cord blood cells.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Weissman IL . Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 2000; 287: 1442–1446.
Verfaillie CM . Hematopoietic stem cells for transplantation. Nat Immunol 2002; 3: 314–317.
Storb RF, Champlin R, Riddell SR et al. Non-myeloablative transplants for malignant disease. Hematology. Am Soc Hematol Educ Program 2001; 375–391.
Aversa F, Tabilio A, Velardi A et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.
Barker JN, Davies SM, DeFor T et al. Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. Blood 2001; 97: 2957–2961.
Castro-Malaspina H, Harris RE, Gajewski J et al. Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood 2002; 99: 1943–1951.
Kollman C, Howe CW, Anasetti C et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 2001; 98: 2043–2051.
Drobyski WR, Klein J, Flomenberg N et al. Superior survival associated with transplantation of matched unrelated versus one-antigen-mismatched unrelated or highly human leukocyte antigen-disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts. Blood 2002; 99: 806–814.
Gluckman E . Current status of umbilical cord blood hematopoietic stem cell transplantation. Exp Hematol 2000; 28: 1197–1205.
Laughlin MJ, Barker J, Bambach B et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med 2001; 344: 1815–1822.
Barrett AJ, Ringden O, Zhang MJ et al. Effect of nucleated marrow cell dose on relapse and survival in identical twin bone marrow transplants for leukemia. Blood 2000; 95: 3323–3327.
Gluckman E, Rocha V, Chevret S . Results of unrelated umbilical cord blood hematopoietic stem cell transplant. Transfusion Clin Biol 2001; 8: 146–154.
Mavroudis D, Read E, Cottler-Fox M et al. CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies. Blood 1996; 88: 3223–3229.
Mehta J, Powles R, Horton C et al. Factors affecting engraftment and hematopoietic recovery after unpurged autografting in acute leukemia. Bone Marrow Transplant 1996; 18: 319–324.
Mehta J, Powles R, Treleaven J et al. Number of nucleated cells infused during allogeneic and autologous bone marrow transplantation: an important modifiable factor influencing outcome. Blood 1997; 90: 3808–3810.
Paulin T . Importance of bone marrow cell dose in bone marrow transplantation. Clin Transplant 1992; 6: 48–54.
Rubinstein P, Carrier C, Scaradavou A et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.
Bittencourt H, Rocha V, Chevret S et al. Association of CD34 cell dose with hematopoietic recovery, infections, and other outcomes after HLA-identical sibling bone marrow transplantation. Blood 2002; 99: 2726–2733.
Woolfrey AE, Anasetti C, Storer B et al. Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children. Blood 2002; 99: 2002–2008.
Naughton BA, Naughton GK . Hematopoiesis on nylon mesh templates. Comparative long-term bone marrow culture and the influence of stromal support cells. Ann NY Acad Sci 1989; 554: 125–140.
Caldwell J, Palsson BO, Locey B et al. Culture perfusion schedules influence the metabolic activity and granulocyte–macrophage colony-stimulating factor production rates of human bone marrow stromal cells. J Cell Physiol 1991; 147: 344–353.
Schwartz RM, Emerson SG, Clarke MF et al. In vitro myelopoiesis stimulated by rapid medium exchange and supplementation with hematopoietic growth factors. Blood 1991; 78: 3155–3161.
Schwartz RM, Palsson BO, Emerson SG . Rapid medium perfusion rate significantly increases the productivity and longevity of human bone marrow cultures. Proc Natl Acad Sci USA 1991; 88: 6760–6764.
Haylock DN, To LB, Dowse TL et al. Ex vivo expansion and maturation of peripheral blood CD34+ cells into the myeloid lineage. Blood 1992; 80: 1405–1412.
Kaushansky K . Thrombopoietin and hematopoietic stem cell development. Ann NY Acad Sci 1999; 872: 314–319.
Bhatia M, Wang JC, Kapp U et al. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci USA 1997; 94: 5320–5325.
Bhatia R, McGlave PB, Miller JS et al. A clinically suitable ex vivo expansion culture system for LTC-IC and CFC using stroma-conditioned medium. Exp Hematol 1997; 25: 980–991.
Luens KM, Travis MA, Chen BP et al. Thrombopoietin, kit ligand, and flk2/flt3 ligand together induce increased numbers of primitive hematopoietic progenitors from human CD34+Thy-1+Lin- cells with preserved ability to engraft SCID-hu bone. Blood 1998; 91: 1206–1215.
Petzer AL, Hogge DE, Landsdorp PM et al. Self-renewal of primitive human hematopoietic cells (long-term-culture-initiating cells) in vitro and their expansion in defined medium. Proc Natl Acad Sci USA 1996; 93: 1470–1474.
Piacibello W, Sanavio F, Severino A et al. Engraftment in nonobese diabetic severe combined immunodeficient mice of human CD34(+) cord blood cells after ex vivo expansion: evidence for the amplification and self-renewal of repopulating stem cells. Blood 1999; 93: 3736–3749.
Conneally E, Cashman J, Petzer A et al. Expansion in vitro of transplantable human cord blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity in nonobese diabetic-scid/scid mice. Proc Natl Acad Sci USA 1997; 94: 9836–9841.
Dao MA, Hashino K, Kato I et al. Adhesion to fibronectin maintains regenerative capacity during ex vivo culture and transduction of human hematopoietic stem and progenitor cells. Blood 1998; 92: 4612–4621.
Hoffman R . Progress in the development of systems for in vitro expansion of human hematopoietic stem cells. Curr Opin Hematol 1999; 6: 184–191.
McNiece I, Briddell R . Ex vivo expansion of hematopoietic progenitor cells and mature cells. Exp Hematol 2001; 29: 3–11.
Naparstek E, Hardan Y, Ben-Shahar M et al. Enhanced marrow recovery by short preincubation of marrow allografts with human recombinant interleukin-3 and granulocyte–macrophage colony-stimulating factor. Blood 1992; 80: 1673–1678.
Brugger W, Heimfeld S, Berenson RJ et al. Reconstitution of hematopoiesis after high-dose chemotherapy by autologous progenitor cells generated ex vivo. N Engl J Med 1995; 333: 283–287.
Kanz L, Brugger W . Retraction: reconstitution of hematopoiesis after high-dose chemotherapy by autologous progenitor cells generated ex vivo. N Engl J Med 2001; 345: 64.
Williams SF, Lee WJ, Bender JG et al. Selection and expansion of peripheral blood CD34+ cells in autologous stem cell transplantation for breast cancer. Blood 1996; 87: 1687–1691.
Alcorn MJ, Holyoake TL, Richmond L et al. CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity. J Clin Oncol 1996; 14: 1839–1847.
Holyoake TL, Alcorn MJ, Richmond L et al. CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens. Bone Marrow Transplant 1997; 19: 1095–1101.
Paquette RL, Dergham ST, Karpf E et al. Ex vivo expanded unselected peripheral blood: progenitor cells reduce posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast cancer. Blood 2000; 96: 2385–2390.
Reiffers J, Cailliot C, Dazey B et al. Abrogation of post-myeloablative chemotherapy neutropenia by ex-vivo expanded autologous CD34-positive cells. Lancet 1999; 354: 1092–1093.
McNiece I, Jones R, Bearman SI et al. Ex vivo expanded peripheral blood progenitor cells provide rapid neutrophil recovery after high-dose chemotherapy in patients with breast cancer. Blood 2000; 96: 3001–3007.
Stiff P, Chen B, Franklin W et al. Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer. Blood 2000; 95: 2169–2174.
Spooncer E, Heyworth CM, Dunn A et al. Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors. Differentiation 1986; 31: 111–118.
Engelhardt M, Douville J, Behringer D et al. Hematopoietic recovery of ex vivo perfusion culture expanded bone marrow and unexpanded peripheral blood progenitors after myeloablative chemotherapy. Bone Marrow Transplant 2001; 27: 249–259.
Lundell BI, Vredenburgh JJ, Tyer C et al. Ex vivo expansion of bone marrow from breast cancer patients: reduction in tumor cell content through passive purging. Bone Marrow Transplant 1998; 22: 153–159.
Hanania EG, Giles RE, Kavanagh J et al. Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy. Proc Natl Acad Sci USA 1996; 93: 15346–15351.
Hesdorffer C, Ayello J, Ward M et al. Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation. J Clin Oncol 1998; 16: 165–172.
Brandt JE, Bartholomew AM, Fortman JD et al. Ex vivo expansion of autologous bone marrow CD34(+) cells with porcine microvascular endothelial cells results in a graft capable of rescuing lethally irradiated baboons. Blood 1999; 94: 106–113.
Guenechea G, Segovia JC, Albella B et al. Delayed engraftment of nonobese diabetic/severe combined immunodeficient mice transplanted with ex vivo-expanded human CD34(+) cord blood cells. Blood 1999; 93: 1097–1105.
Peters SO, Kittler EL, Ramshaw HS et al. Ex vivo expansion of murine marrow cells with interleukin-3 (IL-3), IL-6, IL-11, and stem cell factor leads to impaired engraftment in irradiated hosts. Blood 1996; 87: 30–37.
Harrison DE, Astle CM . Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure. J Exp Med 1982; 156: 1767–1779.
Tisdale JF, Hanazono Y, Sellers SE et al. Ex vivo expansion of genetically marked rhesus peripheral blood progenitor cells results in diminished long-term repopulating ability. Blood 1998; 92: 1131–1141.
Szilvassy SJ, Meyerrose TE, Ragland PL et al. Homing and engraftment defects in ex vivo expanded murine hematopoietic cells are associated with downregulation of beta1 integrin. Exp Hematol 2001; 29: 1494–1502.
Koller MR, Manchel I, Maher RJ et al. Clinical-scale human umbilical cord blood cell expansion in a novel automated perfusion culture system. Bone Marrow Transplant 1998; 21: 653–663.
Adkins D, Spitzer G, Johnston M et al. Transfusions of granulocyte-colony-stimulating factor-mobilized granulocyte components to allogeneic transplant recipients: analysis of kinetics and factors determining posttransfusion neutrophil and platelet counts. Transfusion 1997; 37: 737–748.
Adkins DR, Goodnough LT, Shenoy S et al. Effect of leukocyte compatibility on neutrophil increment after transfusion of granulocyte colony-stimulating factor-mobilized prophylactic granulocyte transfusions and on clinical outcomes after stem cell transplantation. Blood 2000; 95: 3605–3612.
Barrett J, Childs R . New directions in allogeneic stem cell transplantation. Semin Hematol 2002; 39: 1–2.
McSweeney PA, Niederwieser D, Shizuru JA et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.
Rocha V, Cornish J, Sievers EL et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962–2971.
Cairo MS, Wagner JE . Placental and/or umbilical cord blood: an alternative source of hematopoietic stem cells for transplantation. Blood 1997; 90: 4665–4678.
Barker JN, Weisdorf DJ, DeFor TE et al. Impact of multiple unit unrelated donor umbilical cord blood transplantation in adults: preliminary analysis of safety and efficacy. Blood 2001; 98: 2791.
Stiff P, Pecora A, Parthasarathy M et al. Umbilical cord blood transplants in adults using a combination of unexpanded and ex vivo expanded cells: preliminary clinical observations. Blood 1998; 92: 646a.
Shpall EJ, Quinones R, Hami L et al. Transplantation of cancer patients receiving high dose chemotherapy with ex vivo expanded cord blood cells. Blood 1998; 92: 646a.
Jaroscak J, Martin PL, Waters-Pick B et al. A phase I trial of augmentation of unrelated umbilical cord blood transplantation with ex-vivo expanded cells. Blood 1998; 92: 646a.
Pecora AL, Stiff P, Jennis A et al. Prompt and durable engraftment in two older adult patients with high risk chronic myelogenous leukemia (CML) using ex vivo expanded and unmanipulated unrelated umbilical cord blood. Bone Marrow Transplant 2000; 25: 797–799.
Eaves C, Zandstra P, Conneally E et al. Changes in the cytokine regulation of stem cell self-renewal during ontogeny. Stem Cells 1998; 16 (Suppl. 1): 177–184.
Holyoake TL, Nicolini FE, Eaves CJ . Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow. Exp Hematol 1999; 27: 1418–1427.
Lansdorp PM . Developmental changes in the function of hematopoietic stem cells. Exp Hematol 1995; 23: 187–191.
Nicolini FE, Holyoake TL, Cashman JD et al. Unique differentiation programs of human fetal liver stem cells shown both in vitro and in vivo in NOD/SCID mice. Blood 1999; 94: 2686–2695.
Oh IH, Lau A, Eaves CJ . During ontogeny primitive (CD34(+)CD38(−)) hematopoietic cells show altered expression of a subset of genes associated with early cytokine and differentiation responses of their adult counterparts. Blood 2000; 96: 4160–4168.
Zandstra PW, Conneally E, Piret JM et al. Ontogeny-associated changes in the cytokine responses of primitive human haemopoietic cells. Br J Haematol 1998; 101: 770–778.
Rebel VI, Miller CL, Eaves CJ et al. The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their liver adult bone marrow counterparts. Blood 1996; 87: 3500–3507.
Mayani H, Lansdorp PM . Biology of human umbilical cord blood-derived hematopoietic stem/progenitor cells. Stem Cells 1998; 16: 153–165.
Xu R, Reems JA . Umbilical cord blood progeny cells that retain a CD34+ phenotype after ex vivo expansion have less engraftment potential than unexpanded CD34+ cells. Transfusion 2001; 41: 213–218.
Kollet O, Peled A, Byk T et al. beta2 microglobulin-deficient (B2m(null)) NOD/SCID mice are excellent recipients for studying human stem cell function. Blood 2000; 95: 3102–3105.
Rosler ES, Brandt JE, Chute J et al. An in vivo competitive repopulation assay for various sources of human hematopoietic stem cells. Blood 2000; 96: 3414–3421.
Dorrell C, Gan OI, Pereira DS et al. Expansion of human cord blood CD34(+)CD38(−) cells in ex vivo culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: dissociation of SRC phenotype and function. Blood 2000; 95: 102–110.
Huang S, Law P, Young D et al. Candidate hematopoietic stem cells from fetal tissues, umbilical cord blood vs. adult bone marrow and mobilized peripheral blood. Exp Hematol 1998; 26: 1162–1171.
Bhatia M, Bonnet D, Kapp U et al. Quantitative analysis reveals expansion of human hematopoietic repopulating cells after short-term ex vivo culture. J Exp Med 1997; 186: 619–624.
Ueda T, Tsuji K, Yoshino H et al. Expansion of human NOD/SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, IL-6, and soluble IL-6 receptor. J Clin Invest 2000; 105: 1013–1021.
Danet GH, Lee HW, Luongo JL et al. Dissociation between stem cell phenotype and NOD/SCID repopulating activity in human peripheral blood CD34(+) cells after ex vivo expansion. Exp Hematol 2001; 29: 1465–1473.
Donaldson C, Denning-Kendall P, Bradley B et al. The CD34(+)CD38(neg) population is significantly increased in haemopoietic cell expansion cultures in serum-free compared to serum-replete conditions: dissociation of phenotype and function. Bone Marrow Transplant 2001; 27: 365–371.
Larochelle A, Vormoor J, Hanenberg H et al. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy. Nat Med 1996; 2: 1329–1337.
Albella B, Segovia JC, Bueren JA . Does the granulocyte–macrophage colony-forming unit content in ex vivo-expanded grafts predict the recovery of the recipient leukocytes? Blood 1997; 90: 464–470.
Dunbar CE, Seidel NE, Doren S et al. Improved retroviral gene transfer into murine and Rhesus peripheral blood or bone marrow repopulating cells primed in vivo with stem cell factor and granulocyte colony-stimulating factor. Proc Natl Acad Sci USA 1996; 93: 11871–11876.
Szilvassy SJ, Meyerrose TE, Ragland PL et al. Differential homing and engraftment properties of hematopoietic progenitor cells from murine bone marrow, mobilized peripheral blood, and fetal liver. Blood 2001; 98: 2108–2115.
Ramirez M, Segovia JC, Benet I et al. Ex vivo expansion of umbilical cord blood (UCB) CD34(+) cells alters the expression and function of alpha 4 beta 1 and alpha 5 beta 1 integrins. Br J Haematol 2001; 115: 213–221.
Levesque JP, Leavesley DI, Niutta S et al. Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins. J Exp Med 1995; 181: 1805–1815.
Hurley RW, McCarthy JB, Verfaillie CM . Direct adhesion to bone marrow stroma via fibronectin receptors inhibits hematopoietic progenitor proliferation. J Clin Invest 1995; 96: 511–519.
Giet O, Huygen S, Beguin Y et al. Cell cycle activation of hematopoietic progenitor cells increases very late antigen-5-mediated adhesion to fibronectin. Exp Hematol 2001; 29: 515–524.
Glimm H, Oh IH, Eaves CJ . Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G(2)/M transit and do not reenter G(0). Blood 2000; 96: 4185–4193.
Andrews RG, Briddell RA, Hill R et al. Engraftment of primates with G-CSF mobilized peripheral blood CD34+ progenitor cells expanded in G-CSF, SCF and MGDF decreases the duration and severity of neutropenia. Stem Cells 1999; 17: 210–218.
Glimm H, Eisterer W, Lee K et al. Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-beta2 microglobulin-null mice. J Clin Invest 2001; 107: 199–206.
Oostendorp RA, Audet J, Eaves CJ . High-resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro and in vivo. Blood 2000; 95: 855–862.
Oostendorp RA, Audet J, Miller C et al. Cell division tracking and expansion of hematopoietic long-term repopulating cells. Leukemia 1999; 13: 499–501.
Gothot A, Pyatt R, McMahel J et al. Functional heterogeneity of human CD34(+) cells isolated in subcompartments of the G0 /G1 phase of the cell cycle. Blood 1997; 90: 4384–4393.
Gothot A, van der Loo JC, Clapp DW et al. Cell cycle-related changes in repopulating capacity of human mobilized peripheral blood CD34(+) cells in non-obese diabetic/severe combined immune-deficient mice. Blood 1998; 92: 2641–2649.
Habibian HK, Peters SO, Hsieh CC et al. The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit. J Exp Med 1998; 188: 393–398.
Summers YJ, Heyworth CM, de Wynter EA et al. Cord blood G(0) CD34+ cells have a thousand-fold higher capacity for generating progenitors in vitro than G(1) CD34+ cells. Stem Cells 2001; 19: 505–513.
Nibley WE, Spangrude GJ . Primitive stem cells alone mediate rapid marrow recovery and multilineage engraftment after transplantation. Bone Marrow Transplant 1998; 21: 345–354.
Zijlmans JM, Visser JW, Laterveer L et al. The early phase of engraftment after murine blood cell transplantation is mediated by hematopoietic stem cells. Proc Natl Acad Sci USA 1998; 95: 725–729.
Uchida N, Tsukamoto A, He D et al. High doses of purified stem cells cause early hematopoietic recovery in syngeneic and allogeneic hosts. J Clin Invest 1998; 101: 961–966.
Vose JM, Bierman PJ, Lynch JC et al. Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with recurrent indolent non-Hodgkin's lymphoma. Biol Blood Marrow Transplant 2001; 7: 680–687.
Negrin RS, Atkinson K, Leemhuis T et al. Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer. Biol Blood Marrow Transplant 2000; 6: 262–271.
Moore MA . Umbilical cord blood: an expandable resource. J Clin Invest 2000; 105: 855–856.
Takenaka K, Nagafuji K, Harada M et al. In vitro expansion of hematopoietic progenitor cells induces functional expression of Fas antigen (CD95). Blood 1996; 88: 2871–2877.
Karanu FN, Murdoch B, Gallacher L et al. The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med 2000; 192: 1365–1372.
Varnum-Finney B, Purton LE, Yu M et al. The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells. Blood 1998; 91: 4084–4091.
Peled T, Landau E, Prus E et al. Cellular copper content modulates differentiation and self-renewal in cultures of cord blood-derived CD34+ cells. Br J Haematol 2002; 116: 655–661.
Cheng T, Rodrigues N, Shen H et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 2000; 287: 1804–1808.
Giannola DM, Shlomchik WD, Jegathesan M et al. Hematopoietic expression of HOXB4 is regulated in normal and leukemic stem cells through transcriptional activation of the HOXB4 promoter by upstream stimulating factor (USF)-1 and USF-2. J Exp Med 2000; 192: 1479–1490.
Ohneda O, Fennie C, Zheng Z et al. Hematopoietic stem cell maintenance and differentiation are supported by embryonic aorta-gonad-mesonephros region-derived endothelium. Blood 1998; 92: 908–919.
Majumdar MK, Thiede MA, Mosca JD et al. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 1998; 176: 57–66.
Pittenger MF, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–147.
McNiece I, Harrington JA, James RI et al. Ex vivo expansion of cord blood cells without CD34 selection using co-culture on MSC. Blood 2001; 98: 3537.
Kraus M, Pang L, Wilder P . Selective expansion of distinct populations in umbilical cord blood using various antibody cocktail selection strategies. Blood 2001; 98: 5118.
Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145–1147.
Kaufman DS, Hanson ET, Lewis RL et al. Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci USA 2001; 98: 10716–10721.
Takatoku M, Sellers S, Agricola BA, Metzger ME, Kato I, Donahue RE, and Dunbar CE . Avoidance of stimulation improves engraftment of cultured and retrovirally transduced hematopoietic cells in primates. J Clin Invest 2001; 108: 447–455.
About this article
Cite this article
Devine, S., Lazarus, H. & Emerson, S. Clinical application of hematopoietic progenitor cell expansion: current status and future prospects. Bone Marrow Transplant 31, 241–252 (2003). https://doi.org/10.1038/sj.bmt.1703813
- bone marrow transplantation
- stem cells
Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform
Scientific Reports (2016)
Inhibition of p38 MAPK activity promotes ex vivo expansion of human cord blood hematopoietic stem cells
Annals of Hematology (2012)
Hematopoietic reconstitution of CD34+ cells derived from short-term cultured cord blood mononuclear cells
Biotechnology and Bioprocess Engineering (2009)
Ex vivo expansion of CD34+ and T and NK cells from umbilical cord blood for leukemic BALB/C nude mouse transplantation
International Journal of Hematology (2008)