Effects of Eupalinilide E and UM171, alone and in combination on cytokine stimulated ex-vivo expansion of human cord blood hematopoietic stem cells

Blood Cells Mol Dis. 2020 Sep;84:102457. doi: 10.1016/j.bcmd.2020.102457. Epub 2020 Jun 1.

Abstract

Eupalinilide E was assessed for ex-vivo expansion activity on hematopoietic stem cells (HSCs) from human cord blood (CB) CD34+ cells in serum-free, SCF, TPO and FL stimulated 7 day cultures. Eupalinilide E ex-vivo enhanced phenotyped (p) HSCs and glycolysis of CD34+ cells isolated 7 days after culture as measured by extracellular acidification rate, but did not alone show enhanced NSG engrafting capability of HSCs as determined by chimerism and numbers of SCID Repopulating cells, a quantitative measure of functional human HSCs. This is another example of pHSCs not necessarily recapitulating functional activity of these cells. Lack of effect on engrafting HSCs may be due to a number of possibilities, including down regulation of CXCR4 or of the homing capacity of these treated cells. However, Eupalinilide did act in an additive to synergistic fashion with UM171 to enhance ex vivo expansion of both pHSCs, and functionally engrafting HSCs. While reasons for the disconnect between pHSC and function of HSCs with Eupalinilide E alone cultured CB CD34+ cells is yet to be determined, the data suggest possible future use of Eupalinilide and UM171 together to enhance ex vivo production of CB HSCs for clinical hematopoietic cell transplantation.

Keywords: Eupalinilide E; Ex vivo expansion; Glycolysis; Hematopoietic stem cells; UM171.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD34 / analysis
  • Cell Culture Techniques
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / pharmacology
  • Fetal Blood / cytology*
  • Fetal Blood / drug effects
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Indoles / pharmacology*
  • Mice
  • Mice, SCID
  • Pyrimidines / pharmacology*
  • Sesquiterpenes / pharmacology*

Substances

  • Antigens, CD34
  • Cytokines
  • Indoles
  • Pyrimidines
  • Sesquiterpenes
  • UM171 compound
  • eupalinilide E