title: Mesenchymal stem cells enhance xenochimerism in NK-depleted hosts.
abstract: BACKGROUND
  Xenogeneic hematopoietic engraftment holds promise as a strategy to achieve whole organ xenograft tolerance. We tested whether xenogeneic bone marrow grafts, engineered with mesenchymal stem cells (MSCs), might provide a new nontoxic approach to enhance xenogeneic engraftment.
  
  
  METHODS
  ACI rat MSCs, cultured from whole bone marrow, were identified as CD29+ CD44+OX-18+, CD45-HIS36- and could differentiate into adipogenic and osteogenic tissue. Lethally irradiated B6 mice received ACI whole bone marrow either alone or in combination with ACI MSC. Xenogeneic engraftment was measured in murine peripheral blood on days 7, 50, and 100. Natural killer (NK)-cell-depleted murine recipients treated with or without MSC underwent rat skin graft transplants on the day of the bone marrow infusion.
  
  
  RESULTS
  In NK-depleted hosts, control animals failed to survive 60 days; 40% MSC-treated hosts survived >100 days, P < 0 .05. Rat hematopoietic engraftment exceeded 89% on days 7 and 54 and decreased to <25% by day 100. No graft-versus-host disease was observed in MSC-treated animals, P < 0.05. Skin graft survival was prolonged in the MSC-treated group, (21 +/- 1.7 days, P = 0.2).
  
  
  CONCLUSIONS
  Our findings present a new approach in engineering xenografts and provide an encouraging platform for additional studies.
authors.affiliation: Department of Surgery, Chicago, IL 60612, USA.
authors.forename: Ada
authors.initials: A
authors.lastname: Moadsiri
authors.forename: David
authors.initials: D
authors.lastname: Polchert
authors.forename: Kristyn
authors.initials: K
authors.lastname: Genrich
authors.forename: Phyllis
authors.initials: P
authors.lastname: Napoles
authors.forename: Eduardo
authors.initials: E
authors.lastname: Reina
authors.forename: Julius
authors.initials: J
authors.lastname: Turian
authors.forename: Brett
authors.initials: B
authors.lastname: Smith
authors.forename: Amelia
authors.initials: A
authors.lastname: Bartholomew
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D046528:Chimerism; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D007694:Killer Cells, Natural / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011912:Rats, Inbred ACI; D016038:Skin Transplantation; D014183:Transplantation, Heterologous / Q000276:immunology / Q000379:methods*