Clinical-scale production of granulocyte progenitor and post-progenitor cells using daniplestim, leridistim, Progenipoietin, Promegapoietin and autologous plasma

S. D. Patel, R. Guo, W. M. Miller, E. T. Papoutsakis, N. I. Minster, C. M. Baum, J. N. Winter*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: Supplementation of PBC autografts with ex vivo expanded PBMC may significantly reduce or eliminate the period of neutropenia associated with high-dose chemotherapy. Methods: Unmanipulated growth-factor mobilized PBMC were expanded in media containing daniplestim, leridistim, Promegapoietin, and Progenipoietin (DLPP) and 2% autologous plasma at 4 X 105 PBMC/mL, first in 25 cm2 T-flasks, with sampling on Days 7, 10, 13 and 15, and then in 1264 cm2 Nunclon Cell Factories, with sampling on Days 7 and 13. Results: In T25-flasks, amximal CFU-GM expansion ([38.2 ± 9.5]-fold) occurred on Day 10, whereas maximal total cell expansion ([6.7 ± 1.1]-fold) occurred on Day 15. Production of CD15+CD11b- and CD15+CD11b+ granulocytic post-progenitors (3.0 ± 0.4 X 106 and 3.7 ± 0.9 X 106, respectively) was also maximal at Day 15. Compared with the previously studied combination of Flt3L, PIXY321, G-CSF, GM-CSF and Epo, the DLPP cocktail performed similarly, with the exception of yielding larger GM colonies at Day 10 and fewer granulocyte post-progenitors on Day 15. In Cell Factories, CFU-GM were expanded (31.6 ± 14.5)-fold, while total nonadherent cells were expanded (2.6 ± 0.5)-fold. The two stack Cell Factory cultures seeded with 1.0 x 108 unselected PBMC produced approximately 3.3 x 106 CFU-GM and 1.3 X 108 myeloid post-progenitors. Discussion: Whereas expansion of cell numbers, CFU-GM and granulocytic post-progenitors in Cell Factories mirrored that achieved in T25-flasks, future preclinical studies with the DLPP cytokine combination may be performed in small volumes, with subsequent translation to the larger volume Cell Factories. Sufficient expansion can be achieved using the DLPP cytokine combination in the Cell Factories to provide the numbers of progenitors required for clinical trials.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalCytotherapy
Volume2
Issue number2
DOIs
StatePublished - Jan 1 2000

Keywords

  • Autologous stem cell transplantation
  • Ex vivo expansion
  • Granulocyte progenitors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

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