Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation

Blood. 2013 Oct 24;122(17):3074-81. doi: 10.1182/blood-2013-05-503177. Epub 2013 Aug 30.


Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates, and early mortality. 16,16-Dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis, and we hypothesized that brief ex vivo modulation with dmPGE2 could improve patient outcomes by increasing the "effective dose" of HSCs. Molecular profiling approaches were used to determine the optimal ex vivo modulation conditions (temperature, time, concentration, and media) for use in the clinical setting. A phase 1 trial was performed to evaluate the safety and therapeutic potential of ex vivo modulation of a single UCB unit using dmPGE2 before reduced-intensity, double UCB transplantation. Results from this study demonstrated clear safety with durable, multilineage engraftment of dmPGE2-treated UCB units. We observed encouraging trends in efficacy, with accelerated neutrophil recovery (17.5 vs 21 days, P = .045), coupled with preferential, long-term engraftment of the dmPGE2-treated UCB unit in 10 of 12 treated participants.

Trial registration: NCT00890500.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 16,16-Dimethylprostaglandin E2 / pharmacology*
  • Adult
  • Aged
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / immunology
  • Cells, Cultured
  • Cord Blood Stem Cell Transplantation / methods*
  • Cryopreservation
  • Female
  • Fetal Blood / cytology
  • Fetal Blood / drug effects*
  • Fetal Blood / immunology
  • Fetal Blood / transplantation
  • Gene Expression Profiling
  • Graft Survival / immunology*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Transplantation Chimera
  • Transplantation, Homologous
  • Treatment Outcome


  • 16,16-Dimethylprostaglandin E2

Associated data