Experimental Hematology
Volume 34, Issue 11 , Pages 1573-1582 , November 2006

Primitive hematopoietic cell populations reside in the spleen: Studies in the pig, baboon, and human

  • Frank J.M.F. Dor

      Affiliations

    • Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA
    • Department of Surgery, Erasmus MC, Rotterdam, The Netherlands
    • ,
  • Mario L. Ramirez

      Affiliations

    • Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA
    • ,
  • Kalindi Parmar

      Affiliations

    • Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass., USA
    • ,
  • Erica L. Altman

      Affiliations

    • Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA
    • ,
  • Christene A. Huang

      Affiliations

    • Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA
    • ,
  • Julian D. Down

      Affiliations

    • Genetix Pharmaceuticals, Inc., Cambridge, Mass., USA
    • ,
  • David K.C. Cooper

      Affiliations

    • Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA
    • Corresponding Author InformationOffprint requests to: David K.C. Cooper, M.D., Ph.D., F.R.C.S., Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Biomedical Sciences Tower East, Room E1550A, 200 Lothrop Street, Pittsburgh, PA 15261, USA

Received 30 March 2006 ,Revised 9 June 2006 ,Accepted 23 June 2006.

References 

  1. Taniguchi H, Toyoshima T, Fukao K, et al. Presence of hematopoietic stem cells in the adult liver. Nat Med. 1996;2:198–203
  2. Down JD, White-Scharf ME. Reprogramming immune responses: enabling cellular therapies and regenerative medicine. Stem Cells. 2003;21:21–32
  3. Sykes M. Mixed chimerism and transplant tolerance. Immunity. 2001;14:417–424
  4. Schwarze ML, Menard MT, Fuchimoto Y, et al. Mixed hematopoietic chimerism induces long-term tolerance to cardiac allografts in miniature swine. Ann Thorac Surg. 2000;70:131–138
  5. Fuchimoto Y, Huang CA, Yamada K, et al. Mixed chimerism and tolerance without whole body irradiation in a large animal model. J Clin Invest. 2000;105:1779–1789
  6. Kuhr CS, Allen MD, Junghanss C, et al. Tolerance to vascularized kidney grafts in canine mixed hematopoietic chimeras. Transplantation. 2002;73:1487–1492
  7. Kawai T, Cosimi AB, Colvin RB, et al. Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys. Transplantation. 1995;59:256–262
  8. Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen–matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism. Transplantation. 1999;68:480–484
  9. Dor FJMF, Gollackner B, Cooper DKC. Can spleen transplantation induce tolerance? A review of the literature. Transpl Int. 2003;16:451–460
  10. Gollackner B, Dor FJMF, Knosalla C, et al. Spleen transplantation in miniature swine: surgical technique and results in MHC-matched donor and recipient pairs. Transplantation. 2003;75:1799–1806
  11. Dor FJMF, Tseng Y-L, Kuwaki K, et al. Immunological unresponsiveness in chimeric miniature swine following MHC-mismatched spleen transplantation. Transplantation. 2005;80:1791–1804
  12. Kodama S, Huhtreiber W, Fujimura S, Dale EA, Faustman DL. Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science. 2003;302:1223–1227
  13. Sachs DH. MHC homozygous miniature swine. In:  Swindle MM,  Moody DC,  Phillips LD editor. Swine as Models in Biomedical Research. Ames: Iowa State University Press; 1992;p. 3–15
  14. Pescovitz MD, Lunney JK, Sachs DH. Preparation and characterization of monoclonal antibodies reactive with porcine PBL. J Immunol. 1984;133:368–375
  15. Hammerberg C, Churig CG. The culturing of pig peripheral blood lymphocytes in microelisa wells for the direct measurement of a specific antibody response. Vet Immunol Immunopathol. 1984;7:139–152
  16. Huang CA, Lorf T, Arn JS, Koo GC, Blake T, Sachs DH. Characterization of a monoclonal anti-porcine CD3 antibody. Xenotransplantation. 1999;6:201–212
  17. Pescovitz MD, Lunney JK, Sachs DH. Murine anti-swine T4 and T8 monoclonal antibodies: distribution and effects on proliferative and cytotoxic T cells. J Immunol. 1985;134:37–44
  18. Heinz M, Huang CA, Emery DW, et al. Use of CD9 expression to enrich for porcine hematopoietic progenitors. Exp Hematol. 2002;30:809–815
  19. Dato ME, Wierda WG, Kim YB. A triggering structure recognized by G7 monoclonal antibody on porcine lymphocytes and granulocytes. Cell Immunol. 1992;140:468–477
  20. Saalmuller A, Aasted B, Canals A, et al. Analyses of mAb reactive with porcine CD8. Vet Immunol Immunopathol. 1994;43:249–254
  21. Goodell MA, Rosenzweig M, Kim H, et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med. 1997;3:1337–1345
  22. Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183:1797–1806
  23. LeGuern AC, Giovino MA, Abe M, et al. Stem cell activity of porcine c-kit+ hematopoietic cells. Exp Hematol. 2003;31:833–840
  24. Emery DW, Sachs DH, LeGuern C. Culture and characterization of hematopoietic progenitor cells from miniature swine. Exp Hematol. 1996;24:927–935
  25. Emery DW, Holley K, Sachs DH. Enhancement of swine progenitor chimerism in mixed swine/human bone marrow cultures with swine cytokines. Exp Hematol. 1999;27:1330–1337
  26. Breems DA, Blokland EA, Neben S, Ploemacher RE. Frequency analysis of human primitive haematopoietic stem cell subsets using a cobblestone area forming cell assay. Leukemia. 1994;8:1095–1104
  27. Buhler LH, Awwad M, Treter S, et al. Pig hematopoietic cell chimerism in baboons conditioned with a nonmyeloablative regimen and CD154 blockade. Transplantation. 2002;73:12–22
  28. Shin IS, Nam MJ, Park SJ, Youn HY, Han HR. Cloning of canine GM-CSF and SCF genes. J Vet Sci. 2001;2:159–166
  29. Down JD, Awwad M, Kurilla-Mahon B, et al. Increases in autologous hematopoietic progenitors in the blood of baboons following irradiation and treatment with porcine stem cell factor and interleukin-3. Transplant Proc. 2000;32:1045–1046
  30. Okada S, Nakauchi H, Nagayoshi K, et al. Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule. Blood. 1991;78:1706–1712
  31. De Jong MO, Wagemaker G, Wognum AW. Separation of myeloid and erythroid progenitors based on expression of CD34 and c-kit. Blood. 1995;86:4076–4085
  32. Huss R, Hong DS, McSweeney PA, Hoy CA, Deeg HJ. Differentiation of canine bone marrow cells with hemopoietic characteristics from an adherent stromal cell precursor. Proc Natl Acad Sci U S A. 1995;92:748–752
  33. Ody C, Corbel C, Dunon D, Vainio O, Imhof BA. MHC class II and c-kit expression allows rapid enrichment of T cell progenitors from total bone marrow cells. Blood. 2000;96:3988–3990
  34. Rehakova Z, Trebichavsky I, Sinkora J, Splichal I, Sinkora M. Early ontogeny of monocytes and macrophages in the pig. Physiol Res. 1998;47:357–363
  35. Ploemacher R. Cobblestone area forming cell (CAFC) assay. In:  Freshney RI,  Pragnell IB,  Freshney MG editor. Culture of Hemopoietic Cells. New York: Wiley-Liss Inc; 1994;p. 1–21
  36. Sanchez MJ, Holmes A, Miles C, Dzierzak E. Characterization of the first hematopoietic stem cells in the AGM and liver of the mouse embryo. Immunity. 1996;5:513–525
  37. Marshall CJ, Trasher AJ. The embryonic origins of human hematopoiesis. Br J Haematol. 2001;112:838–850
  38. Freedman MH, Saunders EF. Hematopoiesis in the human spleen. Am J Hematol. 1981;11:271–275
  39. Slayton WB, Georgelas A, Pierce LJ, et al. The spleen is a major site of megakaryopoiesis following transplantation of murine hematopoietic stem cells. Blood. 2002;100:3975–3982
  40. Ohno H, Ogawa M, Nishikawa S, Hayashi S, Kunisada R. Conditions required for myelopoiesis in murine spleen. Immunol Lett. 1993;35:197–204
  41. Yanai N, Satoh T, Obinata M. Endothelial cells create a hematopoietic inductive microenvironment preferential to erythropoiesis in the mouse spleen. Cell Struct Funct. 1991;16:87–93
  42. Jacobsen LO, Marks EK, Rolson NJ, Gaston EO, Zirkle RE. The effect of spleen protection on mortality following ex-irradiation. J Lab Clin Med. 1949;34:1538–1543
  43. Wolber FM, Leonard E, Michael S, Orschell-Traycoff CM, Yoder MC, Srour EF. Roles of spleen and liver in development of the murine hematopoietic system. Exp Hematol. 2002;30:1010–1019
  44. Kraus MD, Bartlett NL, Fleming MD, Dorfman DM. Splenic pathology in meylodysplasia: a report of 13 cases with clinical correlation. Am J Surg Pathol. 1998;22:1255–1266
  45. Thiele J, Kvasnicka HM, Czieslick C. CD34+ progenitor cells in idiopathic (primary) myelofibrosis: a comparative quantification between spleen and bone marrow tissue. Ann Hematol. 2002;81:86–89
  46. Haverson K, Bailey M, Stokes CR, et al. Monoclonal antibodies raised to human cells—specificity for pig leukocytes. Vet Immunol Immunopathol. 2001;80:175–186
  47. Kersey JH, LeBien TW, Abramson CS, Newman R, Sutherland R, Greaves M. P-24: a human leukemia–associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody. J Exp Med. 1981;153:726–731
  48. Uchida N, Fujisaki T, Eaves AC, Eaves CJ. Transplantable hematopoietic stem cells in human fetal liver have a CD34− side population (SP) phenotype. J Clin Invest. 2001;108:1071–1077
  49. Nadin BM, Goodell MA, Hirschi KK. Phenotype and hematopoietic potential of side population cells throughout embryonic development. Blood. 2003;102:2436–2443
  50. Guo Y, Follo M, Geiger K, Lubbert M, Engelhardt M. Side-population cells from different precursor compartments. J Hematother Stem Cell Res. 2003;12:71–82
  51. Parmar K, Burdick D, Ethier M, et al. Murine side population cells contain cobblestone area–forming cell activity in mobilized blood. Stem Cells Dev. 2005;14:452–461
  52. Robinson SN, Seina SM, Gohr JC, Kuszynski CA, Sharp JG. Evidence for a qualitative hierarchy within the Hoechst-33342 ‘side population’ (SP) of murine bone marrow cells. Bone Marrow Transplant. 2005;35:807–818
  53. Pearce DJ, Ridler CM, Simpson C, et al. Multiparameter analysis of murine bone marrow side population cells. Blood. 2004;103:2541–2546
  54. Matsuzaki Y, Kinjo K, Mulligan RC, et al. Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. Immunity. 2004;20:87–93
  55. Meytes D, Ortega JA, Ma A, Wald BR, Shore NA, Dukes PP. The relationship between human spleen and blood erythroid burst forming units (BFU-E). Br J Haematol. 1983;55:347–356
  56. Soderdahl G, Tammik C, Remberger M, Ringden O. Cadaveric bone marrow and spleen cells for transplantation. Bone Marrow Transplant. 1998;21:79–84
  57. Conneally E, Cashman J, Petzer A, Eaves C. 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 U S A. 1997;94:9836–9841
  58. Van Hennik PB, Verstegen MM, Bierhuizen MF, et al. Highly efficient transduction of the green fluorescent protein gene in human umbilical cord blood stem cells capable of cobblestone formation in long-term cultures and multilineage engraftment of immunodeficient mice. Blood. 1998;92:4013–4022
  59. Hao QL, Thiemann FT, Petersen D, Smogorzewska EM, Crooks GM. Extended long-term culture reveals a highly quiescent and primitive human hematopoietic progenitor population. Blood. 1996;88:3306–3313

PII: S0301-472X(06)00411-5

doi: 10.1016/j.exphem.2006.06.016

Experimental Hematology
Volume 34, Issue 11 , Pages 1573-1582 , November 2006

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