Expansion and homing of umbilical cord blood hematopoietic stem and progenitor cells for clinical transplantation

Biol Blood Marrow Transplant. 2015 Jun;21(6):1008-19. doi: 10.1016/j.bbmt.2014.12.022. Epub 2014 Dec 30.

Abstract

The successful expansion of hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood (UCB) for transplantation could revolutionize clinical practice by improving transplantation-related outcomes and making available UCB units that have suboptimal cell doses for transplantation. New cytokine combinations appear able to promote HSPC growth with minimal differentiation into mature precursors and new agents, such as insulin-like growth factor-binding protein 2, are being used in clinical trials. Molecules that simulate the HSPC niche, such as Notch ligand, have also shown promise. Further improvements have been made with the use of mesenchymal stromal cells, which have made possible UCB expansion without a potentially deleterious prior CD34/CD133 cell selection step. Chemical molecules, such as copper chelators, nicotinamide, and aryl hydrocarbon antagonists, have shown excellent outcomes in clinical studies. The use of bioreactors could further add to HSPC studies in future. Drugs that could improve HSPC homing also appear to have potential in improving engraftment times in UCB transplantation. Technologies to expand HSPC from UCB and to enhance the homing of these cells appear to have attained the goal of accelerating hematopoietic recovery. Further discoveries and clinical studies are likely to make the goal of true HSPC expansion a reality for many applications in future.

Keywords: Clinical trials; Engraftment; Ex vivo expansion; Hematopoietic stem and progenitor cells; Hematopoietic stem cell transplantation; Umbilical cord blood.

Publication types

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

MeSH terms

  • Bioreactors
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Clinical Trials as Topic
  • Cord Blood Stem Cell Transplantation
  • Cytokines / pharmacology
  • Ethylenediamines / pharmacology
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / immunology*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / pharmacology
  • Intracellular Signaling Peptides and Proteins / pharmacology
  • Membrane Proteins / pharmacology
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology*
  • Niacinamide / pharmacology
  • Receptors, Aryl Hydrocarbon / antagonists & inhibitors
  • Receptors, Aryl Hydrocarbon / immunology
  • Stem Cell Niche / immunology*

Substances

  • Cytokines
  • Ethylenediamines
  • IGFBP2 protein, human
  • Insulin-Like Growth Factor Binding Protein 2
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Aryl Hydrocarbon
  • delta protein
  • Niacinamide
  • tetraethylenepentamine