Vascular endothelium changes after conditioning in hematopoietic stem cell transplantation: role of cyclophosphamide and busulfan

Transplant Proc. 2010 Sep;42(7):2720-4. doi: 10.1016/j.transproceed.2010.04.024.

Abstract

Vascular endothelial injury, a feature of some complications of hematopoietic stem cell transplantation (HSCT), is characterized by increased endothelial cells. We investigated that classical pretreatment drugs in HSCT could result in vascular endothelial injury in mice. Six-to eight-week-old female BALB/c mice were divided into a control group, a cyclophosphamide group (60 mg/kg per day for 2 days) and a busulfan group (4 mg/kg per day for 4 days). We observed the general state of health and regularly counted the number of white blood cells. Circulating endothelial cells and their progenitors were estimated by flow cytometry. Morphologic endothelial changes were analyzed with optical and transmission electron microscopy. After conditioning with cyclophosphamide or busulfan, white blood cells fell to a low number with injuries noted on hematoxylin and eosin-stained pathology sections. Circulating endothelial cells and their progenitors peaked significantly higher than in the control group. Vascular endothelial injuries were observed in the 2 experimental groups by transmission electron microscopy. These data support the hypothesis the vascular endothelial injury occurs during conditioning with cyclophosphamide or busulfan for HSCT, with simultaneous mobilization of endothelial progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD / immunology
  • Busulfan / pharmacology*
  • Cadherins / immunology
  • Cyclophosphamide / pharmacology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology*
  • Female
  • Glycoproteins / immunology
  • Hematopoietic Stem Cell Mobilization / methods
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Immunosuppressive Agents / pharmacology
  • Leukocyte Common Antigens / immunology
  • Mice
  • Mice, Inbred BALB C
  • Peptides / immunology
  • Rats
  • Transplantation Conditioning / methods

Substances

  • AC133 Antigen
  • Antibodies, Monoclonal
  • Antigens, CD
  • Cadherins
  • Glycoproteins
  • Immunosuppressive Agents
  • Peptides
  • cadherin 5
  • Cyclophosphamide
  • Leukocyte Common Antigens
  • Busulfan