Regulation of early hematopoiesis in serum-derpived cultures of mafosfamide-treated and untreated CD34-enriched bone marrow cultures

O. G. Ottmann, C. C. Stella, M. Eder, P. Reutzel, S. Strocker, D. Hoelzer, A. Ganser

Research output: Contribution to journalArticlepeer-review

Abstract

Our experiments have addressed the regulation of early hematopoietic progenitor cell expansion by interleukin 3 (IL-3) and interleukin 1β (IL-1β) and its modulation by bone marrow fibroblasts in vitro. In a two-stage assay utilizing serum-deprived (SD) presuspension cultures of CD34-enriched bone marrow (BM) cells followed by clonal cultures, absolute numbers of granulocyte-macrophage progenitor cells (day-14 granulocyte-macrophage colony-forming units [CFU-GM]) increased progressively to 164% and 204% of input levels after 12 days of culture in the presence of IL-3 alone or in combination with IL-1β, respectively. Multilineage (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) and erythroid (erythroid burst-forming units, BFU-E) progenitor cell numbers increased above or were maintained at input levels after 4 and 7 days of liquid culture in the presence of IL-3 and Il-3 plus IL-1β, respectively, but in contrast to granulocyte-macrophage colony-forming units (CFU-GM) they were essentially undetectable after 12 days of culture. Progenitors more primitive than colony-forming cells (pre-CFU) were assessed in SD-presuspension cultures of CD34-enriched BM cells purged with mafosfamide to eliminate baseline CFU-GM, CFU-GEMM, and BFU-E. Under these conditions and in the absence of stromal elements, CFU-GM but neither CFU-GEMM nor BFU-E developed in response to cytokines alone. In the additional presence of passaged bone marrow fibroblasts, however, IL-3 plus IL-1β and to a lesser degree IL-3 alone induced a pronounced amplification of BFU-E and CFU-GEMM, indicating that their development from a more primitive progenitor compartment requires growth activities in addition to IL-3 and IL-1β that are provided by marrow-derived stromal cells such as fibroblasts.

Original languageEnglish
Pages (from-to)773-778
Number of pages6
JournalExperimental Hematology
Volume19
Issue number8
Publication statusPublished - 1991

Keywords

  • Colony-stimulating factors
  • Fibroblasts
  • Interleukin 1
  • Interleukin 3
  • Mafosfamide
  • Pre-CFU
  • Progenitor amplification
  • Serum-deprived culture

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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