Different growth factor requirements for the ex vivo amplification of transplantable human cord blood cells in a NOD/SCID mouse model

S. Bruno, L. Gammaitoni, M. Gunetti, F. Sanavio, F. Fagioli, M. Aglietta, W. Piacibello

Research output: Contribution to journalArticlepeer-review

Abstract

The growth factor combination containing early acting cytokines FLT-3 ligand (FL), Stem Cell Factor (SCF) and thrombopoietin (TPO) is able to maintain, for an extended culture period, early stem cells, defined as long-term repopulating NOD/SCID mice (Scid Repopulating Cell-SRC) contained in cord blood (CB). In this culture system, the role of IL-6 and IL-3 has not been clearly established. Using a combination of FL+TPO+SCF with or without IL-6, we were able to form CB CD34+ cells for 30 weeks. The CB CD34+ cells cultured in this system engrafted NOD/SCID mice after 6 weeks of culture; the cells from primary recipients were also able to engraft secondary NOD/SCID mice. When CB CD34+ cells were cultured in the presence of IL-3 in the place of IL-6 we observed an even better expansion of cells and a similar clonogenic progenitor output in the first 8 weeks of culture. However, more primitive LTC-IC output increased up to week 6 with the growth factor combination containing IL-3 and then decreased and disappeared, while with the growth factor combination with or without IL-6 increased up to week 23. Cells cultured for 4 weeks with the 4-factor combination containing IL-3 engrafted NOD/SCID mice less efficiently. Repopulation of NOD/SCID mice was no longer observed when ex vivo expansion was performed for 6 weeks. This study provides some evidence that no differences could be detected in long-term maintenance and even expansion of human primitive cord blood cells cultured with FL+TPO+SCF in the presence or absence of IL-6. Under the culture conditions employed in this study, the presence of IL-3 reduced the repopulating potential of expanded CB CD34+ cells.

Original languageEnglish
Pages (from-to)38-48
Number of pages11
JournalJournal of Biological Regulators and Homeostatic Agents
Volume15
Issue number1
Publication statusPublished - 2001

Keywords

  • Cord blood
  • Cytokines
  • Expansion
  • Long-term culture
  • NOD/SCID mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Endocrinology
  • Physiology
  • Immunology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)

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