Antioxidant N-acetyl-L-cysteine increases engraftment of human hematopoietic stem cells in immune-deficient mice

Blood. 2014 Nov 13;124(20):e45-8. doi: 10.1182/blood-2014-03-559369. Epub 2014 Oct 6.

Abstract

Immunocompromised mice, such as the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, have been widely used to examine the self-renewal and differentiation potential of human hematopoietic stem cells (HSCs) in vivo. However, the efficiency of human HSC engraftment remains very low. Here, we report that NOD/SCID mice had higher levels of reactive oxygen species (ROS) in their bone marrow (BM) than other commonly used mouse strains (C57BL/6 and BALB/C). Treatment with the antioxidant N-acetyl-l-cysteine (NAC) decreased ROS levels in the BM of NOD/SCID mice. Furthermore, the NAC-treated mice displayed a significant increase in human HSC engraftment and multilineage hematopoietic differentiation in the mice. In comparison with the control mice, NAC-treated recipients displayed a 10.8-fold increase in hematopoietic engraftment in the injected tibiae. A beneficial effect of NAC for human hematopoietic engraftment was also observed in an additional immunodeficient mouse strain, namely NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NOD/SCID/γc(-/-) or NSG). Thus, this study uncovers a previously unappreciated negative effect of ROS on human stem cell engraftment in immunodeficient mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use*
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Bone Marrow / drug effects*
  • Bone Marrow / metabolism
  • Female
  • Hematopoiesis / drug effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, SCID
  • Reactive Oxygen Species / metabolism*
  • Transplantation, Heterologous

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Acetylcysteine