Persistent decrease in proliferative potential of marrow CD34(+)cells exposed to early-acting growth factors after autologous bone marrow transplantation

Bone Marrow Transplant. 2002 Apr;29(7):557-62. doi: 10.1038/sj.bmt.1703512.

Abstract

Post-graft hematopoiesis is characterized by long-term quantitative deficiency in marrow progenitor cells in both autologous and allogenic settings. In order to evaluate the function of post-graft progenitor cells, the proliferative capacity of marrow CD34(+) cells was evaluated in 10 patients 6 months after autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma and compared to that of 10 patients before ABMT and 10 normal controls. Immuno-selected CD34(+) cells were cultured for 7 days in liquid serum-free medium with a combination of early-acting GF consisting of stem cell factor, IL-3 and IL-1beta. Clonogenic efficiency of unselected cells for CFU-GM and BFU-E was decreased in post-graft patients compared to pre-graft and control patients. However, clonogenic efficiency of selected CD34(+) cells for CFU-GM was not different in post-graft, pre-graft and control patients but BFU-E values of post-graft patients remained lower than those of control patients. Decreased percentages of CD34(+) CD38(-) cells were observed in both post-graft and pre-graft patients while those of CD34(+) c-kit(+) cells were similar in all three patient groups. After 7-day liquid culture, expansion yields of total progenitor cells were significantly lower in post-graft patients (147 +/- 28%) than in pre-graft (255 +/- 27%) and control patients (246 +/- 23%). Post-graft deficiency in progenitor cell expansion was particularly marked for BFU-E (61 +/- 24%) compared to pre-graft patients (220 +/- 82%) and to controls (349 +/- 82%). These results indicate impaired proliferative potential of marrow CD34(+) cells several months after ABMT involving erythroid progenitor cells and/or commitment towards erythroid lineage from a more immature stage (pre-CFU).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD34 / analysis
  • Bone Marrow Transplantation*
  • Cell Division / drug effects
  • Cells, Cultured / drug effects
  • Colony-Forming Units Assay
  • Culture Media, Serum-Free
  • Erythroid Precursor Cells / drug effects
  • Erythroid Precursor Cells / pathology
  • Female
  • Hematopoiesis / drug effects*
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Immunophenotyping
  • Interleukin-1 / pharmacology*
  • Interleukin-3 / pharmacology*
  • Lymphoma, Non-Hodgkin / therapy
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-kit / analysis
  • Stem Cell Factor / pharmacology*
  • Transplantation, Autologous

Substances

  • Antigens, CD34
  • Culture Media, Serum-Free
  • Interleukin-1
  • Interleukin-3
  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit