CD34+ enriched cell products intended for autologous transendocardial CD34+ cell transplantation release significant amounts of angiopoietin-1

Transfus Clin Biol. 2019 Nov;26(4):273-278. doi: 10.1016/j.tracli.2019.01.005. Epub 2019 Jan 14.

Abstract

Objectives: Cell-based therapy has emerged as a promising strategy for the treatment of patients with heart failure. Increasing evidence supports the hypothesis that paracrine mechanisms mediated by soluble factors released by the cells play a predominate role in reparative processes. The aim of our study was to analyze which cytokines are released by CD34+ enriched cell products intended for autologous transendocardial CD34+ cell transplantation in patients with cardiomyopathy.

Material and methods: The peripheral blood CD34+ cells from 12 patients were mobilized with granulocyte colony-stimulating factor, collected via apheresis and enriched by immunoselection.

Results: In CD34+ enriched cell population, hematopoietic, but not mesenchymal or endothelial, progenitors were detected. Except for angiopoietin-1, other measured cytokines (FGF1, FGF2, VEGF, PDGF, IL-6, HGH, SDF-1α/CXCL12, NRG1) were not released by CD34+ cells. The average concentration of angiopoietin-1 released by 5×106 CD34+ cells grown in neutral DMEM medium was 213.6±130.0pg/mL (range: 74-448pg/mL). Angiopoietin-1 secretion correlated well with CD34+ cell's capacity for generating colonies derived from hematopoietic progenitors (Pearson's correlation=0.964; P<0.001).

Conclusion: Our study presents angiopoietin-1 as an interesting candidate and suggests future studies to explore how its release by CD34+ cells might impact the success of autologous CD34+ cell transplantation.

Keywords: Angiopoetin-1; Angiopoïétine-1; CD34(+) cell; Cell-based therapy; Cellules CD34 +; Cytokine; Heart failure; Insuffisance cardiaque; Thérapie basée sur les cellules.

MeSH terms

  • Adult
  • Angiopoietin-1 / blood*
  • Antigens, CD34 / analysis*
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Cytokines / analysis
  • Heart Failure / etiology
  • Heart Failure / therapy
  • Hemangioblasts / chemistry
  • Hemangioblasts / cytology
  • Hemangioblasts / metabolism
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / chemistry
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Ischemia / complications
  • Neovascularization, Physiologic
  • Transplantation, Autologous

Substances

  • ANGPT1 protein, human
  • Angiopoietin-1
  • Antigens, CD34
  • Cytokines