Sources of Human and Murine Hematopoietic Stem Cells

Mitchell E. Horwitz1

1 Duke University Medical Center, Durham, North Carolina
Publication Name:  Current Protocols in Immunology
Unit Number:  Unit 22A.2
DOI:  10.1002/0471142735.im22a02s79
Online Posting Date:  November, 2007
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


This unit describes various sites from which human and murine hematopoietic stem cells (HSC) can be collected, including bone marrow, peripheral blood, and, in the case of human HSC, umbilical cord blood. Guidelines related to each of the cell harvesting procedures are described, and a discussion of the expected populations of cells harvested from these various sites is included. Cell products can be composed of a combination of true HSC, lineage‐committed hematopoietic progenitor cells, and terminally differentiated fully mature cells. While use of steady‐state peripheral blood as a source of HSC is the most convenient approach, yields of these cells are very low. However, mobilization methods that stimulate movement of stem cells out of the bone marrow into peripheral blood significantly increase HSC yields. Use of G‐CSF has been accepted as the standard method for stem cell mobilization. The unit describes a variety of investigational cytokines and chemokines that have been shown to mobilize human stem including interleukin 3, 11, and 8, flt‐3 ligand, and stem cell factor. Curr. Protoc. Immunol. 79:22A.2.1‐22A.2.6. © 2007 by John Wiley & Sons, Inc.

Keywords: hematopoietic stem cells; bone marrow; peripheral blood; umbilical cord blood; stem cell mobilization

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Human HSC Procurement
  • Murine HSC Procurement
  • Literature Cited
  • Tables
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
   Ballen, K.K., Wilson, M., Wuu, J., Ceredona, A.M., Hsieh, C., Stewart, F.M., Popovsky, M.A., and Quesenberry, P.J. 2001. Bigger is better: Maternal and neonatal predictors of hematopoietic potential of umbilical cord blood units. Bone Marrow Transplant. 27:7‐14.
   Bensinger, W.I., Martin, P.J., Storer, B., Clift, R., Forman, S.J., Negrin, R., Kashyap, A., Flowers, M.E., Lilleby, K., Chauncey, T.R., Storb, R., and Appelbaum, F.R. 2001. Transplantation of bone marrow as compared with peripheral‐blood cells from HLA‐identical relatives in patients with hematologic cancers. N. Engl. J. Med. 344:175‐181.
   Briddell, R.A., Hartley, C.A., Smith, K.A., and McNiece, I.K. 1993. Recombinant rat stem cell factor synergizes with recombinant human granulocyte colony‐stimulating factor in vivo in mice to mobilize peripheral blood progenitor cells that have enhanced repopulating potential. Blood 82:1720‐1723.
   Champlin, R.E., Schmitz, N., Horowitz, M.M., Chapuis, B., Chopra, R., Cornelissen, J.J., Gale, R.P., Goldman, J.M., Loberiza, F.R. Jr., Hertenstein, B., Klein, J.P., Montserrat, E., Zhang, M.J., Ringden, O., Tomany, S.C., Rowlings, P.A., Van Hoef, M.E., and Gratwohl, A. 2000. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation: IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). Blood 95:3702‐3709.
   Fibbe, W.E., Hamilton, M.S., Laterveer, L.L., Kibbelaar, R.E., Falkenburg, J.H., Visser, J.W., and Willemze, R. 1992. Sustained engraftment of mice transplanted with IL‐1‐primed blood‐derived stem cells. J. Immunol. 148:417‐421.
   Fleischman, R.A., Custer, R.P., and Mintz, B. 1982. Totipotent hematopoietic stem cells: Normal self‐renewal and differentiation after transplantation between mouse fetuses. Cell 30:351‐359.
   Gaddy, J, Pierluigi, P., and Broxmeyer, H.E. 2000. Clinical and basic science studies of human umbilical cord blood: Implications for the GVL effect following cord blood transplantation. In Allogeneic Immunotherapy for Malignant Diseases ( Y.‐Z. Jiang and J. Barrett, eds.) pp. 267‐284. Marcel Dekker, New York.
   Georges, G.E., Sandmaier, B.M., and Storb, R. 1998. Blood stem cell transplantation. In Animal Models (J. Reiffers and J. Armitage, eds.) pp. 1‐17. Mosby, London.
   Grzegorzewski, K.J., Komschlies, K.L., Jacobsen, S.E., Ruscetti, F.W., Keller, J.R., and Wiltrout, R.H. 1995. Mobilization of long‐term reconstituting hematopoietic stem cells in mice by recombinant human interleukin 7. J. Exp. Med. 181:369‐374.
   Hao, Q.L., Shah, A.J., Thiemann, F.T., Smogorzewska, E.M., and Crooks, G.M. 1995. A functional comparison of CD34 + CD38‐ cells in cord blood and bone marrow. Blood 86:3745‐3753.
   Laterveer, L., Lindley, I.J., Hamilton, M.S., Willemze, R., and Fibbe, W.E. 1995. Interleukin‐8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long‐term myelolymphoid repopulating ability. Blood 85:2269‐2275.
   Lord, B.I., Woolford, L.B., Wood, L.M., Czaplewski, L.G., McCourt, M., Hunter, M.G., and Edwards, R.M. 1995. Mobilization of early hematopoietic progenitor cells with BB‐10010: A genetically engineered variant of human macrophage inflammatory protein‐1 alpha. Blood 85:3412‐3415.
   Mauch, P., Lamont, C., Neben, T.Y., Quinto, C., Goldman, S.J., and Witsell, A. 1995. Hematopoietic stem cells in the blood after stem cell factor and interleukin‐11 administration: Evidence for different mechanisms of mobilization. Blood 86:4674‐4680.
   Micklem, H.S., Ford, C.E., Evans, E.P., Ogden, D.A., and Papworth, D.S. 1972. Competitive in vivo proliferation of foetal and adult haematopoietic cells in lethally irradiated mice. J. Cell. Physiol. 79:293‐298.
   Miller, J.S., McCullar, V., Punzel, M., Lemischka, I.R., and Moore, K.A. 1999. Single adult human CD34(+)/Lin‐/CD38(–) progenitors give rise to natural killer cells, B‐lineage cells, dendritic cells, and myeloid cells. Blood 93:96‐106.
   Mohty, M., Kuentz, M., Michallet, M., Bourhis, J.H., Milpied, N., Sutton, L., Jouet, J.P., Attal, M., Bordigoni, P., Cahn, J.Y., Boiron, J.M., and Blaise, D. 2002. Chronic graft‐versus‐host disease after allogeneic blood stem cell transplantation: Long‐term results of a randomized study. Blood 100:3128‐3134.
   Molineux, G., Pojda, Z., Hampson, I.N., Lord, B.I., and Dexter, T.M. 1990. Transplantation potential of peripheral blood stem cells induced by granulocyte colony‐stimulating factor. Blood 76:2153‐2158.
   Morrison, S.J. and Weissman, I.L. 1994. The long‐term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1:661‐673.
   Morrison, S.J., Hemmati, H.D., Wandycz, A.M., and Weissman, I.L. 1995. The purification and characterization of fetal liver hematopoietic stem cells. Proc. Natl. Acad. Sci. U.S.A. 92:10302‐10306.
   Neben, S., Marcus, K., and Mauch, P. 1993. Mobilization of hematopoietic stem and progenitor cell subpopulations from the marrow to the blood of mice following cyclophosphamide and/or granulocyte colony‐stimulating factor. Blood 81:1960‐1967.
   Powles, R., Mehta, J., Kulkarni, S., Treleaven, J., Millar, B., Marsden, J., Shepherd, V., Rowland, A., Sirohi, B., Tait, D., Horton, C., Long, S., and Singhal, S. 2000. Allogeneic blood and bone‐marrow stem‐cell transplantation in haematological malignant diseases: A randomised trial. Lancet 355:1231‐1237.
   Smith, L.G., Weissman, I.L., and Heimfeld, S. 1991. Clonal analysis of hematopoietic stem‐cell differentiation in vivo. Proc. Natl. Acad. Sci. U.S.A. 88:2788‐2792.
   Sudo, Y., Shimazaki, C., Ashihara, E., Kikuta, T., Hirai, H., Sumikuma, T., Yamagata, N., Goto, H., Inaba, T., Fujita, N., and Nakagawa, M. 1997. Synergistic effect of FLT‐3 ligand on the granulocyte colony‐stimulating factor–induced mobilization of hematopoietic stem cells and progenitor cells into blood in mice. Blood 89:3186‐3191.
   Suzuki, H., Okano, A., Suzuki, C., Konishi, A., Akiyama, Y., Ishibashi, T., Ozawa, K., and Asano, S. 1995. A synergistic increase in transplantable peripheral blood stem cells in mice by co‐administration of recombinant human interleukin 6 and recombinant human granulocyte colony‐stimulating factor. Transplantation 59:1596‐1600.
   Wang, J., Kimura, T., Asada, R., Harada, S., Yokota, S., Kawamoto, Y., Fujimura, Y., Tsuji, T., Ikehara, S., and Sonoda, Y. 2003. SCID‐repopulating cell activity of human cord blood‐derived CD34‐ cells assured by intra‐bone marrow injection. Blood 101:2924‐2931.
PDF or HTML at Wiley Online Library