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The Simulation of Hematopoiesis

Implications for the Gene Therapy of Lysosomal Enzyme Disorders
  • Janis L. Abkowitz
  • Monica T. Persik
  • Sandra N. Catlin
  • Peter Guttorp

Abstract

Although the hematopoietic stem cell is an attractive target cell for gene transfer, little is known about its biology in vivo in large animals (or man). We have studied the in vivo behavior of hematopoietic stem cells in glucose-6-phosphate dehydrogenase (G6PD) heterozygous (female Safari) cats, and demonstrated that clonal instability persists for up to 4.5 years after autologous marrow transplantation. This contrasts the 2–6 months of clonal disequilibrium reported in comparable murine studies. Our data also suggests that hematopoietic stem cells do not self-renew more frequently than once per three weeks. These data may impact strategies for optimizing gene therapy in large animals, and by extension in man.

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References

  1. 1.
    . Lemischka IR: The haematopoietic stem cell and its clonal progeny: mechanisms regulating the hierarchy of primitive haematopoietic cells. Cancer Surveys 15: 3, 1992PubMedGoogle Scholar
  2. 2.
    . Spangrude GJ: Characteristics of the hematopoietic stem cell compartment in adult mice. Int. J. Cell Cloning 10: 277, 1992PubMedCrossRefGoogle Scholar
  3. 3.
    . Uchida N, Fleming WH, Alpern EJ, Weissman IL: Heterogeneity of hematopoietic stem cells. Current Opinion in Immunol. 5: 177, 1993CrossRefGoogle Scholar
  4. 4.
    . Ogawa M: Differentiation and proliferation of hematopoietic stem cells. Blood 81: 2844, 1993.PubMedGoogle Scholar
  5. 5.
    . Orlic D, Bodine DM: What defines a pluripotent hematopoietic stem cell (PHSC): will the real PHSC please stand up! Blood 84: 3991, 1994PubMedGoogle Scholar
  6. 6.
    . Jordan CT, Lemischka IR: Clonal and systemic analysis of long-term hematopoiesis in the mouse. Gen. Dev. 4: 220, 1990Google Scholar
  7. 7.
    . Abkowitz JL, Ott RL, Nakamura JM, Steiman L, Fialkow PJ, Adamson JW: Feline G-6-PD cellular mosaicism: application to the study of retrovirus-induced pure red cell aplasia. J. Clin. Invest. 75: 133, 1985PubMedCrossRefGoogle Scholar
  8. 8.
    . Abkowitz JL, Linenberger ML, Newton MF, Ott RL, Guttorp P: Evidence for the maintenance of hematopoiesis in a large animal by the sequential activation of stem cell clones. Proc. Natl. Acad. Sci. USA 87: 9062, 1990PubMedCrossRefGoogle Scholar
  9. 9.
    . Abkowitz JL, Persik MT, Shelton GH, Ott RL, Kiklevich JV, Catlin SN, Guttorp P: The behavior of hematopoietic stem cells in a large animal. Proc. Natl. Acad. Sci. USA 92: 2031, 1995PubMedCrossRefGoogle Scholar
  10. 10.
    . Abkowitz JL, Catlin SN, Guttorp P: Evidence that hematopoiesis may be a stochastic process in vivo. Submitted.Google Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Janis L. Abkowitz
    • 1
    • 2
  • Monica T. Persik
    • 1
  • Sandra N. Catlin
    • 1
  • Peter Guttorp
    • 1
  1. 1.Departments of Medicine and StatisticsUniversity of WashingtonSeattleUSA
  2. 2.Hematology, Room K136CUniversity of WashingtonSeattleUSA

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