Rapid thymic reconstitution following bone marrow transplantation in neonatal mice is VEGF-dependent

Biol Blood Marrow Transplant. 2012 May;18(5):683-9. doi: 10.1016/j.bbmt.2012.01.006. Epub 2012 Jan 25.


Age-related differences in thymic function influence the rapidity of T cell reconstitution following hematopoietic stem cell transplantation (HSCT). In adults, thymic reconstitution is delayed until after marrow engraftment is established, and is significantly improved by approaches that increase marrow chimerism, such as pretransplantation irradiation. In contrast, we show that neonatal mice undergo more rapid and efficient thymic reconstitution than adults, even when bone marrow (BM) engraftment is minimal and in the absence of pretransplantation radiation. We have previously shown that the neonatal thymus produces high levels of vascular endothelial growth factor (VEGF) that drives angiogenesis locally. In this report, we show that inhibition of VEGF prior to HSCT prevents rapid thymic reconstitution in neonates, but has no effect on thymic reconstitution in adults. These data suggest that the early radiation-independent thymic reconstitution unique to the neonatal host is mediated through VEGF, and reveals a novel pathway that might be targeted to improve immune reconstitution post-HSCT.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Bone Marrow Transplantation*
  • Graft Survival
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Microscopy, Confocal
  • Neovascularization, Physiologic
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage
  • Receptors, Vascular Endothelial Growth Factor / adverse effects
  • Receptors, Vascular Endothelial Growth Factor / immunology
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / radiation effects
  • Thymocytes / drug effects
  • Thymocytes / immunology*
  • Thymocytes / radiation effects
  • Thymus Gland / blood supply
  • Thymus Gland / drug effects
  • Thymus Gland / immunology*
  • Thymus Gland / radiation effects
  • Transplantation Chimera
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / immunology
  • Whole-Body Irradiation


  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor