title: Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation.
abstract: BACKGROUND
  Transplantation of myogenic stem cells possesses great potential for long-term repair of dystrophic muscle. In murine-to-murine transplantation experiments, CXCR4 expression marks a population of adult murine satellite cells with robust engraftment potential in mdx mice, and CXCR4-positive murine muscle-derived SP cells home more effectively to dystrophic muscle after intra-arterial delivery in mdx5cv mice. Together, these data suggest that CXCR4 plays an important role in donor cell engraftment. Therefore, we sought to translate these results to a clinically relevant canine-to-canine allogeneic transplant model for Duchenne muscular dystrophy (DMD) and determine if CXCR4 is important for donor cell engraftment.
  
  
  METHODS
  In this study, we used a canine-to-murine xenotransplantation model to quantitatively compare canine muscle cell engraftment, and test the most effective cell population and modulating factor in a canine model of DMD using allogeneic transplantation experiments.
  
  
  RESULTS
  We show that CXCR4 expressing cells are important for donor muscle cell engraftment, yet FACS sorted CXCR4-positive cells display decreased engraftment efficiency. However, diprotin A, a positive modulator of CXCR4-SDF-1 binding, significantly enhanced engraftment and stimulated sustained proliferation of donor cells in vivo. Furthermore, the canine-to-murine xenotransplantation model accurately predicted results in canine-to-canine muscle cell transplantation.
  
  
  CONCLUSIONS
  Therefore, these results establish the efficacy of diprotin A in stimulating muscle cell engraftment, and highlight the pre-clinical utility of a xenotransplantation model in assessing the relative efficacy of muscle stem cell populations.
authors.affiliation: Program in Transplantation Biology, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Mailstop D1-100, Seattle, WA, 98109-1024, USA. mparker@fhcrc.org.
authors.forename: Maura H
authors.initials: MH
authors.lastname: Parker
authors.forename: Carol
authors.initials: C
authors.lastname: Loretz
authors.forename: Ashlee E
authors.initials: AE
authors.lastname: Tyler
authors.forename: Lauren
authors.initials: L
authors.lastname: Snider
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tapscott